Methods for generating databases and databases for identifying polymorphic genetic markers

ABSTRACT

A high throughput method of determining frequencies of genetic variations is provided. The method includes steps of selecting a healthy target population and a genetic variation to be assessed; pooling a plurality of samples of biopolymers obtained from members of the population; determining or detecting the biopolymer that comprises the variation by mass spectrometry; obtaining a mass spectrum or a digital representation thereof; and determining the frequency of the variation in the population.

RELATED APPLICATIONS

[0001] This application is a divisional application of copending U.S.patent application Ser. No. 09/687,483, filed Oct. 13, 2000, to AndreasBraun, Hubert Koster, Dirk Van den Boom, Yip Ping, Charles Rodi, LiyanHe, Norman Chiu and Christian Jurinke entitled “METHODS FOR GENERATINGDATABASES AND DATABASES FOR IDENTIFYING POLYMORPHIC GENETIC MARKERS.”

[0002] Benefit of priority under 35 U.S.C. § 119(e) to the followingprovisional applications is claimed herein:

[0003] U.S. provisional application Serial No. 60/217,658 to AndreasBraun, Hubert Koster; Dirk Van den Boom, filed Jul. 10, 2000, entitled“METHODS FOR GENERATING DATABASES AND DATABASES FOR IDENTIFYINGPOLYMORPHIC GENETIC MARKERS”; U.S. provisional application Serial No.60/159,176 to Andreas Braun, Hubert Koster, Dirk Van den Boom, filedOct. 13, 1999, entitled “METHODS FOR GENERATING DATABASES AND DATABASESFOR IDENTIFYING POLYMORPHIC GENETIC MARKERS”; U.S. provisionalapplication Serial No. 60/217,251, filed Jul. 10, 2000, to AndreasBraun, entitled “POLYMORPHIC KINASE ANCHOR PROTEIN GENE SEQUENCES,POLYMORPHIC KINASE ANCHOR PROTEINS AND METHODS OF DETECTING POLYMORPHICKINASE ANCHOR PROTEINS AND NUCLEIC ACIDS ENCODING THE SAME”. Thisapplication is also a continuation-in-part of U.S. application Ser. No.09/663,968, to Ping Yip, filed Sep. 19, 2000, entitled “METHOD ANDDEVICE FOR IDENTIFYING A BIOLOGICAL SAMPLE.”

[0004] The above-noted applications and provisional applications areincorporated by reference in their entirety.

FIELD OF THE INVENTION

[0005] Process and methods for creating a database of genomic samplesfrom healthy human donors. Methods that use the database to identify andcorrelate with polymorphic genetic markers and other markers withdiseases and conditions are provided.

BACKGROUND

[0006] Diseases in all organisms have a genetic component, whetherinherited or resulting from the body's response to environmentalstresses, such as viruses and toxins. The ultimate goal of ongoinggenomic research is to use this information to develop new ways toidentify, treat and potentially cure these diseases. The first step hasbeen to screen disease tissue and identify genomic changes at the levelof individual samples. The identification of these “disease” markers hasthen fueled the development and commercialization of diagnostic teststhat detect these errant genes or polymorphisms. With the increasingnumbers of genetic markers, including single nucleotide polymorphisms(SNPs), microsatellites, tandem repeats, newly mapped introns and exons,the challenge to the medical and pharmaceutical communities is toidentify genotypes which not only identify the disease but also followthe progression of the disease and are predictive of an organism'sresponse to treatment.

[0007] Currently the pharmaceutical and biotechnology industries find adisease and then attempt to determine the genomic basis for the disease.This approach is time consuming and expensive and in many cases involvesthe investigator guessing as to what pathways might be involved in thedisease.

[0008] Genomics

[0009] Presently the two main strategies employed in analyzing theavailable genomic information are the technology driven reverse geneticsbrute force strategy and the knowledge-based pathway oriented forwardgenetics strategy. The brute force approach yields large databases ofsequence information but little information about the medical or otheruses of the sequence information. Hence this strategy yields intangibleproducts of questionable value. The knowledge-based strategy yieldssmall databases that contain a lot of information about medical uses ofparticular DNA sequences and other products in the pathway and yieldtangible products with a high value.

[0010] Polymorphisms

[0011] Polymorphisms have been known since 1901 with the identificationof blood types. In the 1950's they were identified on the level ofproteins using large population genetic studies. In the 1980's and1990's many of the known protein polymorphisms were correlated withgenetic loci on genomic DNA. For example, the gene dose of theapolipoprotein E type 4 allele was correlated with the risk ofAlzheimer's disease in late onset families (see, e.g., Corder et al.(1993) Science 261: 921-923; mutation in blood coagulation factor V wasassociated with resistance to activated protein C (see, e.g., Bertina etaL. (1994) Nature 369:64-67); resistance to HIV-1 infection has beenshown in Caucasian individuals bearing mutant alleles of the CCR-5chemokine receptor gene (see, e.g., Samson et al. (1996) Nature382:722-725); and a hypermutable tract in antigen presenting cells (APC,such as macrophages), has been identified in familial colorectal cancerin individuals of Ashkenzi jewish background (see, e.g., Laken et al.(1997) Nature Genet. 17:79-83). There can be more than three millionpolymorphic sites in the human genome. Many have been identified, butnot yet characterized or mapped or associated with a marker.

[0012] Single Nucleotide Polymorphisms (SNPs)

[0013] Much of the focus of genomics has been in the identification ofSNPs, which are important for a variety of reasons. They allow indirecttesting (association of haplotypes) and direct testing (functionalvariants). They are the most abundant and stable genetic markers. Commondiseases are best explained by common genetic alterations, and thenatural variation in the human population aids in understanding disease,therapy and environmental interactions.

[0014] Currently, the only available method to identify SNPs in DNA isby sequencing, which is expensive, difficult and laborious. Furthermore,once a SNP is discovered it must be validated to determine if it is areal polymorphism and not a sequencing error. Also, discovered SNPs mustthen be evaluated to determine if they are associated with a particularphenotype. Thus, there is a need to develop new paradigms foridentifying the genomic basis for disease and markers thereof.Therefore, it is an object herein to provide methods for identifying thegenomic basis of disease and markers thereof.

SUMMARY

[0015] Databases and methods using the databases are provided herein.The databases comprise sets of parameters associated with subjects inpopulations selected only on the basis of being healthy (i e., where thesubjects are mammals, such as humans, they are selected based uponapparent health and no detectable infections). The databases can besorted based upon one or more of the selected parameters.

[0016] The databases, for example, can be relational databases, in whichan index that represents each subject serves to relate parameters, whichare the data, such as age, ethnicity, sex, medical history, etc. andultimately genotypic information, that was inputted into and stored inthe database. The database can then be sorted according to theseparameters. Initially, the parameter information is obtained from aquestionnaire answered by each subject from whom a body tissue or bodyfluid sample is obtained. As additional information about each sample isobtained, this information can be entered into the database and canserve as a sorting parameter.

[0017] The databases obtained from healthy individuals have numeroususes, such as correlating known polymorphisms with a phenotype ordisease. The databases can be used to identify alleles that aredeleterious, that are beneficial, and that are correlated with diseases.

[0018] For purposes herein, genotypic information can be obtained by anymethod known to those of skill in the art, but is generally obtainedusing mass spectrometry.

[0019] Also provided herein, is a new use for existing databases ofsubjects and genotypic and other parameters, such as age, ethnicity,race, and gender. Any database can be sorted according to the methodsherein, and alleles that exhibit statistically significant correlationswith any of the sorting parameters can be identified. It is noted,however, is noted, that the databases provided herein and randomlyselected databases will perform better in these methods, sincedisease-based databases suffer numerous limitations, including theirrelatively small size, the homogeneity of the selected diseasepopulation, and the masking effect of the polymorphism associated withthe markers for which the database was selected. Hence, the healthydatabase provided herein, provides advantages not heretofore recognizedor exploited. The methods provided herein can be used with a selecteddatabase, including disease-based databases, with or without sorting forthe discovery and correlation of polymorphisms. In addition, thedatabases provided herein represent a greater genetic diversity than theunselected databases typically utilized for the discovery ofpolymorphisms and thus allow for the enhanced discovery and correlationof polymorphisms.

[0020] The databases provided herein can be used for taking anidentified polymorphism and ascertaining whether it changes in frequencywhen the data are sorted according to a selected parameter.

[0021] One use of these methods is correlating a selected marker with aparticular parameter by following the occurrence of known geneticmarkers and then, having made this correlation, determining oridentifying correlations with diseases. Examples of this use are p53 andLipoprotein Lipase polymorphism. As exemplified herein, known markersare shown to have particular correlation with certain groups, such as aparticular ethnicity or race or one sex. Such correlations will thenpermit development of better diagnostic tests and treatment regimens.

[0022] These methods are valuable for identifying one or more geneticmarkers whose frequency changes within the population as a function ofage, ethnic group, sex or some other criteria. This can allow theidentification of previously unknown polymorphisms and ultimately a geneor pathway involved in the onset and progression of disease.

[0023] The databases and methods provided herein permit, among otherthings, identification of components, particularly key components, of adisease process by understanding its genetic underpinnings and alsopermit an understanding of processes, such as individual drug responses.The databases and methods provided herein also can be used in methodsinvolving elucidation of pathological pathways, in developing newdiagnostic assays, identifying new potential drug targets, and inidentifying new drug candidates.

[0024] The methods and databases can be used with experimentalprocedures, including, but are not limited to, in silico SNPidentification, in vitro SNP identification/verification, geneticprofiling of large populations, and in biostatistical analyses andinterpretations.

[0025] Also provided herein, are combinations that contain a databaseprovided herein and a biological sample from a subject in the database,and typically biological samples from all subjects or a plurality ofsubjects in the database. Collections of the tissue and body fluidsamples are also provided.

[0026] Also, provided herein, are methods for determining a geneticmarker that correlates with age, comprising identifying a polymorphismand determining the frequency of the polymorphism with increasing age ina healthy population.

[0027] Further provided herein are methods for determining whether agenetic marker correlates with susceptibility to morbidity, earlymortality, or morbidity and early mortality, comprising identifying apolymorphism and determining the frequency of the polymorphism withincreasing age in a healthy population.

[0028] Any of the methods herein described can be used out in amultiplex format.

[0029] Also provided are an apparatus and process for accuratelyidentifying genetic information. It is another object herein thatgenetic information be extracted from genetic data in a highly automatedmanner. Therefore, to overcome the deficiencies in the knownconventional systems, methods and apparatus for identifying a biologicalsample are provided.

[0030] Briefly, the method and system for identifying a biologicalsample generates a data set indicative of the composition of thebiological sample. In a particular example, the data set is DNAspectrometry data received from a mass spectrometer. The data set isdenoised, and a baseline is deleted. Since possible compositions of thebiological sample can be known, expected peak areas can be determined.Using the expected peak areas, a residual baseline is generated tofurther correct the data set. Probable peaks are then identifiable inthe corrected data set, which are used to identify the composition ofthe biological sample. In a disclosed example, statistical methods areemployed to determine the probability that a probable peak is an actualpeak, not an actual peak, or that the data too inconclusive to call.

[0031] Advantageously, the method and system for identifying abiological sample accurately makes composition calls in a highlyautomated manner. In such a manner, complete SNP profile information,for example, can be collected efficiently. More importantly, thecollected data are analyzed with highly accurate results. For example,when a particular composition is called, the result can be relied uponwith great confidence. Such confidence is provided by the robustcomputational process employed

DESCRIPTION OF THE DRAWINGS

[0032]FIG. 1 depicts an exemplary sample bank. Panel 1 shows the samplesas a function of sex and ethnicity. Panel 2 shows the Caucasians as afunction of age. Panel 3 shows the Hispanics as a function of age.

[0033]FIGS. 2A and 2C show an age- and sex-distribution of the 291Sallele of the lipoprotein lipase gene in which a total of 436 males and589 females were investigated. FIG. 2B shows an age distribution for the436 males.

[0034]FIG. 3 is an exemplary questionnaire for population-based samplebanking.

[0035]FIG. 4 depicts processing and tracking of blood sample components.

[0036]FIG. 5 depicts the allelic frequency of “sick” alleles and“healthy” alleles as a function of age. It is noted that the relativefrequency of healthy alleles increases in a population with increasingage.

[0037]FIG. 6 depicts the age-dependent distribution of ApoE genotypes(see, Schächter et al. (1994) Nature Genetics 6:29-32).

[0038]FIG. 7A-D depicts age-related and genotype frequency of the p53(tumor suppressor) codon 72 among the Caucasian population in thedatabase. *R72 and *P72 represent the frequency of the allele in thedatabase population. R72, R72P, and P72 represent the genotypes of theindividuals in the population. The frequency of the homozygous P72allele drops from 6.7% to 3.7% with age.

[0039]FIG. 8 depicts the allele and genotype frequencies of the p21 S31Rallele as a function of age.

[0040]FIG. 9 depicts the frequency of the FVII Allele 353Q in pooledversus individual samples.

[0041]FIG. 10 depicts the frequency of the CETP (cholesterol estertransfer protein) allele in pooled versus individual samples.

[0042]FIG. 11 depicts the frequency of the plasminogen activatorinhibitor-1 (PAI-1) 5G in pooled versus individual samples.

[0043]FIG. 12 shows mass spectra of the samples and the ethnic diversityof the PAI-1 alleles.

[0044]FIG. 13 shows mass spectra of the samples and the ethnic diversityof the CETP 405 alleles.

[0045]FIG. 14 shows mass spectra of the samples and the ethnic diversityof the Factor VII 353 alleles.

[0046]FIG. 15 shows ethnic diversity of PAI-1, CETP and Factor VII usingthe pooled DNA samples.

[0047]FIG. 16 shows the p53-Rb pathway and the relationships among thevarious factors in the pathway.

[0048]FIG. 17, which is a block diagram of a computer constructed toprovide and process the databases described herein, depicts a typicalcomputer system for storing and sorting the databases provided hereinand practicing the methods provided herein.

[0049]FIG. 18 is a flow diagram that illustrates the processing stepsperformed using the computer illustrated in FIG. 17, to maintain andprovide access to the databases for identifying polymorphic geneticmarkers.

[0050]FIG. 19 is a histogram showing the allele and genotypedistribution in the age and sex stratified Caucasian population for theAKAP10-1 locus. Bright green bars show frequencies in individualsyounger than 40 years. Dark green bars show frequencies in individualsolder than 60 years.

[0051]FIG. 20 is a histogram showing the allele and genotypedistribution in the age and sex stratified Caucasian population for theAKAP10-5 locus. Bright green bars show frequencies in individualsyounger than 40 years; dark green bars show frequencies in individualsolder than 60 years.

[0052]FIG. 21 is a histogram showing the allele and genotypedistribution in the age and sex stratified Caucasian population for theh-msrA locus. Genotype difference between male age groups issignificant. Bright green bars show frequencies in individuals youngerthan 40 years. Dark green bars show frequencies in individuals olderthan 60 years.

[0053]FIG. 22A-D is a sample data collection questionnaire used for thehealthy database.

[0054]FIG. 23 is a flowchart showing processing performed by thecomputing device of FIG. 24 when performing genotyping of sense strandsand antisense strands from assay fragments.

[0055]FIG. 24 is a block diagram showing a system provided herein;

[0056]FIG. 25 is a flowchart of a method of identifying a biologicalsample provided herein;

[0057]FIG. 26 is a graphical representation of data from a massspectrometer;

[0058]FIG. 27 is a diagram of wavelet transformation of massspectrometry data;

[0059]FIG. 28 is a graphical representation of wavelet stage 0 hi data;

[0060]FIG. 29 is a graphical representation of stage 0 noise profile;

[0061]FIG. 30 is a graphical representation of generating stage noisestandard deviations;

[0062]FIG. 31 is a graphical representation of applying a threshold todata stages;

[0063]FIG. 32 is a graphical representation of a sparse data set;

[0064]FIG. 33 is a formula for signal shifting;

[0065]FIG. 34 is a graphical representation of a wavelet transformationof a denoised and shifted signal;

[0066]FIG. 35 is a graphical representation of a denoised and shiftedsignal;

[0067]FIG. 36 is a graphical representation of removing peak sections;

[0068]FIG. 37 is a graphical representation of generating a peak freesignal;

[0069]FIG. 38 is a block diagram of a method of generating a baselinecorrection;

[0070]FIG. 39 is a graphical representation of a baseline and signal;

[0071]FIG. 40 is a graphical representation of a signal with baselineremoved;

[0072]FIG. 41 is a table showing compressed data;

[0073]FIG. 42 is a flowchart of method for compressing data;

[0074]FIG. 43 is a graphical representation of mass shifting;

[0075]FIG. 44 is a graphical representation of determining peak width;

[0076]FIG. 45 is a graphical representation of removing peaks;

[0077]FIG. 46 is a graphical representation of a signal with peaksremoved;

[0078]FIG. 47 is a graphical representation of a residual baseline;

[0079]FIG. 48 is a graphical representation of a signal with residualbaseline removed;

[0080]FIG. 49 is a graphical representation of determining peak height;

[0081]FIG. 50 is a graphical representation of determiningsignal-to-noise for each peak;

[0082]FIG. 51 is a graphical representation of determining a residualerror for each peak;

[0083]FIG. 52 is a graphical representation of peak probabilities;

[0084]FIG. 53 is a graphical representation of applying an allelic ratioto peak probability;

[0085]FIG. 54 is a graphical representation of determining peakprobability;

[0086]FIG. 55 is a graphical representation of calling a genotype;

[0087]FIG. 56 is a flowchart showing a statistical procedure for callinga genotype;

[0088]FIG. 57 is a flowchart showing processing performed by thecomputing device of FIG. 1 when performing standardless genotyping; and

[0089]FIG. 58 is graphical representation of applying an allelic ratioto peak probability for standardless genotype processing.

DETAILED DESCRIPTION

[0090] Definitions

[0091] Unless defined otherwise, all technical and scientific terms usedherein have the same meaning as is commonly understood by one ofordinary skill in the art to which this invention belongs. All patents,applications, published applications and other publications andsequences from GenBank and other databases referred to herein throughoutthe disclosure are incorporated by reference in their entirety.

[0092] As used herein, a biopolymer includes, but is not limited to,nucleic acid, proteins, polysaccharides, lipids and othermacromolecules. Nucleic acids include DNA, RNA, and fragments thereof.Nucleic acids can be derived from genomic DNA, RNA, mitochondrialnucleic acid, chloroplast nucleic acid and other organelles withseparate genetic material.

[0093] As used herein, morbidity refers to conditions, such as diseasesor disorders, that compromise the health and well-being of an organism,such as an animal. Morbidity susceptibility or morbidity-associatedgenes are genes that, when altered, for example, by a variation innucleotide sequence, facilitate the expression of a specific diseaseclinical phenotype. Thus, morbidity susceptibility genes have thepotential, upon alteration, of increasing the likelihood or general riskthat an organism will develop a specific disease.

[0094] As used herein, mortality refers to the statistical likelihoodthat an organism, particularly an animal, will not survive a fullpredicted lifespan. Hence, a trait or a marker, such as a polymorphism,associated with increased mortality is observed at a lower frequency inolder than younger segments of a population.

[0095] As used herein, a polymorphism, e.g. genetic variation, refers toa variation in the sequence of a gene in the genome amongst apopulation, such as allelic variations and other variations that ariseor are observed. Thus, a polymorphism refers to the occurrence of two ormore genetically determined alternative sequences or alleles in apopulation. These differences can occur in coding and non-codingportions of the genome, and can be manifested or detected as differencesin nucleic acid sequences, gene expression, including, for exampletranscription, processing, translation, transport, protein processing,trafficking, DNA synthesis, expressed proteins, other gene products orproducts of biochemical pathways or in post-translational modificationsand any other differences manifested amongst members of a population. Asingle nucleotide polymorphism (SNP) refers to a polymorphism thatarises as the result of a single base change, such as an insertion,deletion or change in a base.

[0096] A polymorphic marker or site is the locus at which divergenceoccurs. Such site can be as small as one base pair (an SNP). Polymorphicmarkers include, but are not limited to, restriction fragment lengthpolymorphisms, variable number of tandem repeats (VNTR's), hypervariableregions, minisatellites, dinucleotide repeats, trinucleotide repeats,tetranucleotide repeats and other repeating patterns, simple sequencerepeats and insertional elements, such as Alu. Polymorphic forms alsoare manifested as different mendelian alleles for a gene. Polymorphismscan be observed by differences in proteins, protein modifications, RNAexpression modification, DNA and RNA methylation, regulatory factorsthat alter gene expression and DNA replication, and any othermanifestation of alterations in genomic nucleic acid or organellenucleic acids.

[0097] As used herein, a healthy population refers to a population oforganisms, including but are not limited to, animals, bacteria, viruses,parasites, plants, eubacteria, and others, that are disease free. Theconcept of disease-free is a function of the selected organism. Forexample, for mammals it refers to a subject not manifesting any diseasestate. Practically a healthy subject, when human, is defined as humandonor who passes blood bank criteria to donate blood for eventual use inthe general population. These criteria are as follows: free ofdetectable viral, bacterial, mycoplasma, and parasitic infections; notanemic; and then further selected based upon a questionnaire regardinghistory (see FIG. 3). Thus, a healthy population represents an unbiasedpopulation of sufficient health to donate blood according to blood bankcriteria, and not further selected for any disease state. Typically suchindividuals are not taking any medications. For plants, for example, itis a plant population that does not manifest diseases pathologyassociated with plants. For bacteria it is a bacterial populationreplicating without environmental stress, such as selective agents, heatand other pathogens.

[0098] As used herein, a healthy database (or healthy patient database)refers to a database of profiles of subjects that have not beenpre-selected for any particular disease. Hence, the subjects that serveas the source of data for the database are selected, according topredetermined criteria, to be healthy. In contrast to other suchdatabases that have been pre-selected for subjects with a particulardisease or other characteristic, the subjects for the database providedherein are not so-selected. Also, if the subjects do manifest a diseaseor other condition, any polymorphism discovered or characterized shouldbe related to an independent disease or condition. In a one embodiment,where the subjects are human, a healthy subject manifests no diseasesymptoms and meets criteria, such as those set by blood banks for blooddonors.

[0099] Thus, the subjects for the database are a population of anyorganism, including, but are not limited to, animals, plants, bacteria,viruses, parasites and any other organism or entity that has nucleicacid. Among subjects are mammals, such as, although not necessarily,humans. Such a database can capture the diversity of a population, thusproviding for discovery of rare polymorphisms.

[0100] As used herein, a profile refers to information relating to, butnot limited to and not necessarily including all of, age, sex,ethnicity, disease history, family history, phenotypic characteristics,such as height and weight and other relevant parameters. A samplecollect information form is shown in FIG. 22, which illustrates profileintent.

[0101] As used herein, a disease state is a condition or abnormality ordisorder that can be inherited or result from environmental stresses,such as toxins, bacterial, fungal and viral infections.

[0102] As used herein, set of non-selected subjects means that thesubjects have not been pre-selected to share a common disease or othercharacteristic. They can be selected to be healthy as defined herein.

[0103] As used herein, a phenotype refers to a set of parameters thatincludes any distinguishable trait of an organism. A phenotype can bephysical traits and can be, in instances in which the subject is ananimal, a mental trait, such as emotional traits. Some phenotypes can bedetermined by observation elicited by questionnaires (see, e.g., FIGS. 3and 22) or by referring to prior medical and other records. For purposesherein, a phenotype is a parameter around which the database can besorted.

[0104] As used herein, a parameter is any input data that will serve asa basis for sorting the database. These parameters will includephenotypic traits, medical histories, family histories and any othersuch information elicited from a subject or observed about the subject.A parameter can describe the subject, some historical or currentenvironmental or social influence experienced by the subject, or acondition or environmental influence on someone related to the subject.Paramaters include, but are not limited to, any of those describedherein, and known to those of skill in the art.

[0105] As used herein, haplotype refers to two or polymorphism locatedon a single DNA strand. Hence, haplotyping refers to identification oftwo or more polymorphisms on a single DNA strand. Haplotypes can beindicative of a phenotype. For some disorders a single polymorphism cansuffice to indicate a trait; for others a plurality (i.e., a haplotype)can be needed. Haplotyping can be performed by isolating nucleic acidand separating the strands. In addition, when using enzymes such acertain nucleases, that produce, different size fragments from eachstrand, strand separation is not needed for haplotyping.

[0106] As used herein, pattern with reference to a mass spectrum or massspectrometric analyses, refers to a characteristic distribution andnumber of signals (such peaks or digital representations thereof).

[0107] As used herein, signal in the context of a mass spectrum andanalysis thereof refers to the output data, which the number or relativenumber of moleucles having a particular mass. Signals include “peaks”and digital representations thereof.

[0108] As used herein, adaptor, when used with reference to haplotypingusing Fen ligase, refers to a nucleic acid that specifically hybridizesto a polymorphism of interest. An adaptor can be partiallydouble-stranded. An adaptor complex is formed when an adaptor hybridizesto its target.

[0109] As used herein, a target nucleic acid refers to any nucleic acidof interest in a sample. It can contain one or more nucleotides.

[0110] As used herein, standardless analysis refers to a determinationbased upon an internal standard. For example, the frequency of apolymorphism can be determined herein by comparing signals within asingle mass spectrum.

[0111] As used herein, amplifying refers to methods for increasing theamount of a bipolymer, especially nucleic acids. Based on the 5′ and 3′primers that are chosen, amplication also serves to restrict and definethe region of the genome which is subject to analysis. Amplification canbe performed by any method known to those skilled in the art, includinguse of the polymerase chain reaction (PCR) etc. Amplification, e.g., PCRmust be done quantitatively when the frequency of polymorphism isrequired to be determined.

[0112] As used herein, cleaving refers to non-specific and specificfragmentation of a biopolymer.

[0113] As used herein, multiplexing refers to the simultaneous detectionof more than one polymorphism. Methods for performing multiplexedreactions, particularly in conjunction with mass spectrometry are known(see, e.g., U.S. Pat. Nos. 6,043,031, 5,547,835 and International PCTapplication No. WO 97/37041).

[0114] As used herein, reference to mass spectrometry encompasss anysuitable mass spectrometric format known to those of skill in the art.Such formats iniude, but are not limited to, Matrix-Assisted LaserDesorption/Ionization, Time-of-Flight (MALDI-TOF), Electrospray (ES),IR-MALDI (see, e.g., published International PCT application No.99/57318and U.S. Pat. No. 5,118,937), Ion Cyclotron Resonance (ICR), FourierTransform and combinations thereof. MALDI, particular UV and IR, areamong the formats contemplated.

[0115] As used herein, mass spectrum refers to the presentation of dataobtained from analyzing a biopolymer or fragment thereof by massspectrometry either graphically or encoded numerically.

[0116] As used herein, a blood component is a component that isseparated from blood and includes, but is not limited to red blood cellsand platelets, blood clotting factors, plasma, enzymes, plasminogen,immunoglobulins. A cellular blood component is a component of blood,such as a red blood cell, that is a cell. A blood protein is a proteinthat is normally found in blood. Examples of such proteins are bloodfactors VII and VII. Such proteins and components are well-known tothose of skill in the art.

[0117] As used herein, plasma can be prepared by any method known tothose of skill in the art. For example, it can be prepared bycentrifuging blood at a force that pellets the red cells and forms aninterface between the red cells and the buffy coat, which containsleukocytes, above which is the plasma. For example, typical plateletconcentrates contain at least about 10% plasma.

[0118] Blood can be separated into its components, including, but notlimited to, plasma, platelets and red blood cells by any method known tothose of skill in the art. For example, blood can be centrifuged for asufficient time and at a sufficient acceleration to form a pelletcontaining the red blood cells. Leukocytes collect primarily at theinterface of the pellet and supernatant in the buffy coat region. Thesupernatant, which contains plasma, platelets, and other bloodcomponents, can then be removed and centrifuged at a higheracceleration, whereby the platelets pellet.

[0119] As used herein, p53 is a cell cycle control protein that assessesDNA damage and acts as a transcription factor regulation gene whichcontrol cell growth, DNA repair and apoptosis. The p53 mutations havebeen found in a wide variety of different cancers, including all of thedifferent types of leukemia, with varying frequency. The loss of normalp53 functions results in genomic instability and uncontrolled growth ofthe host cell.

[0120] As used herein, p21 is a cyclin-dependent kinase inhibitor,associated with G1 phase arrest of normal cells. Expression triggersapoptosis or programmed cell death and has been associated with Wilms'tumor, a pediatric kidney cancer.

[0121] As used herein, Factor VII is a serine protease involved theextrinsic blood coagulation cascade. This factor is activated bythrombin and works with tissue factor (Factor III) in the processing ofFactor X to Factor Xa. Evidence has supported an association betweenpolymorphisms in the gene and increase Factor VII activity which canresult in an elevated risk of ischemic cardiovascular disease includingmyocardial infarction.

[0122] As used herein, a relational database stores information in aform representative of matrices, such as two-dimensional tables,including rows and columns of data, or higher dimensional matrices. Forexample, in one embodiment, the relational database has separate tableseach with a parameter. The tables are linked with a record number, whichalso acts as an index. The database can be searched or sorted by usingdata in the tables and is stored in any suitable storage medium, such asfloppy disk, CD rom disk, hard drive or other suitable medium.

[0123] As used herein, a bar codes refers any array of opticallyreadable marks of any desired size and shape that are arranged in areference context or frame of, typically, although not necessarily, oneor more columns and one or more rows. For purposes herein, the bar coderefers to any symbology, not necessary “bar” but can include dots,characters or any symbol or symbols.

[0124] As used herein, symbology refers to an identifier code or symbol,such as a bar code, that is linked to a sample. The index will referenceeach such symbology. The symbology is any code known or designed by theuser. The symbols are associated with information stored in thedatabase. For example, each sample can be uniquely identified with anencoded symbology. The parameters, such as the answers to the questionsand subsequent genotypic and other information obtained upon analysis ofthe samples is included in the database and associated with thesymbology. The database is stored on any suitable recording medium, suchas a hard drive, a floppy disk, a tape, a CD ROM, a DVD disk and anyother suitable medium.

[0125] Databases

[0126] Human genotyping is currently dependent on collaborations withhospitals, tissues banks and research institutions that provide samplesof disease tissue. This approach is based on the concept that the onsetand/or progression of diseases can be correlated with the presence of apolymorphisms or other genetic markers. This approach does not considerthat disease correlated with the presence of specific markers and theabsence of specific markers. It is shown herein that identification andscoring of the appearance and disappearance of markers is possible onlyif these markers are measured in the background of healthy subjectswhere the onset of disease does not mask the change in polymorphismoccurrence. Databases of information from disease populations sufferfrom small sample size, selection bias and heterogeneity. The databasesprovided herein from healthy populations solve these problems bypermitting large sample bands, simple selection methods and dilutedheterogeneity.

[0127] Provided herein are first databases of parameters, associatedwith non-selected, particularly healthy, subjects. Also provided arecombinations of the databases with indexed samples obtained from each ofthe subjects. Further provided are databases produced from the firstdatabases. These contain, in addition to the original parameters,information, such as genotypic information, including, but are notlimited to, genomic sequence information, derived from the samples.

[0128] The databases, which are herein designated healthy databases, areso-designated because they are not obtained from subjects pre-selectedfor a particular disease. Hence, although individual members can have adisease, the collection of individuals is not selected to have aparticular disease.

[0129] The subjects from whom the parameters are obtained compriseeither a set of subjects who are randomly selected across, typically,all populations, or are pre-selected to be disease-free or healthy. As aresult, the database is not selected to be representative of anypre-selected phenotype, genotype, disease or other characteristic.Typically the number of subjects from which the database is prepared isselected to produce statistically significant results when used in themethods provided herein. Generally, the number of subjects will begreater than 100, 200, and typically than 1000. The precise number canbe empirically determined based upon the frequency of the parameter(s)that can be used to sort the database. Generally the population can haveat least 50, at least 100, at least 200, at least 500, at least 1000, atleast 5000 or at least 10,000 or more subjects.

[0130] Upon identification of a collection of subjects, informationabout each subject is recorded and associated with each subject as adatabase. The information associated with each of the subjects,includes, but is not limited to, information related to historicalcharacteristics of the subjects, phenotypic characteristics and alsogenotypic characteristics, medical characteristics and any other traitsand characteristics about the subject that can be determined. Thisinformation will serve as the basis for sorting the database.

[0131] In an exemplary embodiment, the subjects are mammals, such ashumans, and the information relates to one or more of parameters, suchas age, sex, medical history, ethnicity and any other factor. Suchinformation, when the animals are humans, for example, can be obtainedby a questionnaire and by observations about the individual, such ashair color, eye color and other characteristics. Genotypic informationcan be obtained from tissue or other body and body fluid samples fromthe subject.

[0132] The healthy genomic database can include profiles andpolymorphisms from healthy individuals from a library of blood sampleswhere each sample in the library is an individual and separate blood orother tissue sample. Each sample in the database is profiled as to thesex, age, ethnic group, and disease history of the donor.

[0133] The databases are generated by first identifying healthypopulations of subjects and obtaining information about each subjectthat will serve as the sorting parameters for the database. Thisinformation can be entered into a storage medium, such as the memory ofa computer.

[0134] The information obtained about each subject in a population usedfor generating the database is stored in a computer memory or othersuitable storage medium. The information is linked to an identifierassociated with each subject. Hence the database will identify asubject, for example by a datapoint representative of a bar code, andthen all information, such as the information from a questionnaire,regarding the individual is associated with the datapoint. As theinformation is collected the database is generated.

[0135] Thus, for example, profile information, such as subject historiesobtained from questionnaires, is collected in the database. Theresulting database can be sorted as desired, using standard software,such as by age, sex and/or ethnicity. An exemplary questionnaire forsubjects from whom samples are to be obtained is shown in FIGS. 22A-D.Each questionnaire, for example, can be identified by a bar code,particularly a machine readable bar code for entry into the database.After a subject provides data and is deemed to be healthy (i.e., meetsstandards for blood donation), the data in the questionnaire is enteredinto the database and is associated with the bar code. A tissue, cell orblood sample is obtained from the subject.

[0136]FIG. 4 exemplifies processing and tracking of blood samplecomponents. Each component is tracked with a bar code, dated, is enteredinto the database and associated with the subject and the profile of thesubject. Typically, the whole blood is centrifuged to produce plasma,red blood cells (which pellet) and leukocytes found in the buffy coatwhich layers in between. Various samples are obtained and coded with abar code and stored for use as needed.

[0137] Samples are collected from the subjects. The samples include, butare not limited to, tissues, cells, and fluids, such as nucleic acid,blood, plasma, amniotic fluid, synovial fluid, urine, saliva, aqueoushumor, sweat, sperm samples and cerebral spinal fluid. It is understoodthat the particular set of samples depends upon the organisms in thepopulation.

[0138] Once samples are obtained the collection can be stored and, insome embodiments, each sample is indexed with an identifier,particularly a machine readable code, such as a bar code. For analyses,the samples or components of the samples, particularly biopolymers andsmall molecules, such as nucleic acids and/or proteins and metabolites,are isolated.

[0139] After samples are analyzed, this information is entered into thedatabase in the memory of the storage medium and associated with eachsubject. This information includes, but is not limited to, genotypicinformation. Particularly, nucleic acid sequence information and otherinformation indicative of polymorphisms, such as masses of PCRfragments, peptide fragment sequences or masses, spectra of biopolymersand small molecules and other indicia of the structure or function of agene, gene product or other marker from which the existence of apolymorphism within the population can be inferred.

[0140] In an exemplary embodiment, a database can be derived from acollection of blood samples. For example, FIG. 1(see, also FIG. 10)shows the status of a collection of over 5000 individual samples. Thesamples were processed in the laboratory following SOP (standardoperating procedure) guidelines. Any standard blood processing protocolcan be used.

[0141] For the exemplary database described herein, the followingcriteria were used to select subjects:

[0142] No testing is done for infectious agents.

[0143] Age: At least 17 years old

[0144] Weight: Minimum of 110 pounds

[0145] Permanently Disqualified:

[0146] History of hepatitis (after age 11)

[0147] Leukemia Lymphoma

[0148] Human immunodeficiency virus (HIV),AIDS

[0149] Chronic kidney disease

[0150] Temporarily Disqualified:

[0151] Pregnancy—until six weeks after delivery, miscarriage or abortion

[0152] Major surgery or transfusions—for one year

[0153] Mononucleosis—until complete recovery

[0154] Prior whole blood donation—for eight weeks

[0155] Antibiotics by injection for one week; by mouth, for forty-eighthours, except antibiotics for skin complexion;

[0156] 5 year Deferment:

[0157] Internal cancer and skin cancer if it has been removed, is healedand there is no recurrence

[0158] These correspond to blood bank criteria for donating blood andrepresent a healthy population as defined herein for a human healthydatabase.

[0159] 5 Structure of the Database

[0160] Any suitable database structure and format known to those ofskill in the art can be employed. For example, a relational database isa an exemplary format in which data are stored as matrices or tables ofthe parameters linked by an indexer that identifies each subject.Software for preparing and manipulating, including sorting the database,can be readily developed or adapted from commercially availablesoftware, such as Microsoft Access.

[0161] Quality Control

[0162] Quality control procedures can be implemented. For example, aftercollection of samples, the quality of the collection in the bank can beassessed. For example, mix-up of samples can be checked by testing forknown markers, such as sex. After samples are separated by ethnicity,samples are randomly tested for a marker associated with a particularethnicity, such as HLA DQA1 group specific component, to assess whetherthe samples have been properly sorted by ethnic group. An exemplarysample bank is depicted in FIG. 4.

[0163] Obtaining Genotypic Data and Other Parameters for the Database

[0164] After informational and historical parameters are entered intothe database, material from samples obtained from each subject, isanalyzed. Analyzed material include proteins, metabolites, nucleicacids, lipids and any other desired constituent of the material. Forexample, nucleic acids, such as genomic DNA, can be analyzed bysequencing.

[0165] Sequencing can be performed using any method known to those ofskill in the art. For example, if a polymorphism is identified or known,and it is desired to assess its frequency or presence among the subjectsin the database, the region of interest from each sample can beisolated, such as by PCR or restriction fragments, hybridization orother suitable method known to those of skill in the art and sequenced.For purposes herein, sequencing analysis can be effected using massspectrometry (see, e.g., U.S. Pat. Nos. 5,547,835, 5,622,824, 5,851,765,and 5,928,906). Nucleic acids also can be sequenced by hybridization(see, e.g., U.S. Pat. Nos. 5,503,980, 5,631,134, 5,795,714) andincluding analysis by mass spectrometry (see, U.S. application Ser. Nos.08/419,994 and 09/395,409).

[0166] In other detection methods, it is necessary to first amplifyprior to identifying the allelic variant. Amplification can beperformed, e.g., by PCR and/or LCR, according to methods known in theart. In one embodiment, genomic DNA of a cell is exposed to two PCRprimers and amplification for a number of cycles sufficient to producethe required amount of amplified DNA. In some embodiments, the primersare located between 150 and 350 base pairs apart.

[0167] Alternative amplification methods include: self sustainedsequence replication (Guatelli, J. C. et al., 1990, Proc. Natl. Acad.Sci. U.S.A. 87:1874-1878), transcriptional amplification system (Kwoh,D. Y. et al., 1989, Proc. Natl. Acad. Sci. U.S.A. 86:1173-1177), Q-BetaReplicase (Lizardi, P. M. et al., 1988, Bio/Technology 6:1197), or anyother nucleic acid amplification method, followed by the detection ofthe amplified molecules using techniques well known to those of skill inthe art. These detection schemes are especially useful for the detectionof nucleic acid molecules if such molecules are present in very lownumbers.

[0168] Nucleic acids also can be analyzed by detection methods andprotocols, particularly those that rely on mass spectrometry (see, e.g.,U.S. Pat. No. 5,605,798, 6,043,031, allowed copending U.S. applicationSer. No. 08/744,481, U.S. application Ser. No. 08/990,851 andInternational PCT application No. WO 99/31278, International PCTapplication No. WO 98/20019). These methods can be automated (see, e.g.,copending U.S. application Ser. No. 09/285,481 and publishedInternational PCT application No. PCT/US00/08111, which describes anautomated process line). Among the methods of analysis herein are thoseinvolving the primer oligo base extension (PROBE) reaction with massspectrometry for detection (described herein and elsewhere, see e.g.,U.S. Pat. No. 6,043,031; see, also U.S. application Ser. Nos.09/287,681, 09/287,682, 09/287,141 and 09/287,679, allowed copendingU.S. application Ser. No. 08/744,481, International PCT application No.PCT/US97/20444, published as International PCT application No. WO98/20019, and based upon U.S. application Ser. Nos. 08/744,481,08/744,590, 08/746,036, 08/746,055, 08/786,988, 08/787,639, 08/933,792,08/746,055, 08/786,988 and 08/787,639; see, also U.S. application Ser.No. 09/074,936, U.S. Pat. No. 6,024,925, and U.S. application Ser. Nos.08/746,055 and 08/786,988, and published International PCT applicationNo. WO 98/20020)

[0169] A chip based format in which the biopolymer is linked to a solidsupport, such as a silicon or silicon-coated substrate, such as in theform of an array, is among the formats for performing the analyses is.Generally, when analyses are performed using mass spectrometry,particularly MALDI, small nanoliter volumes of sample are loaded on,such that the resulting spot is about, or smaller than, the size of thelaser spot. It has been found that when this is achieved, the resultsfrom the mass spectrometric analysis are quantitative. The area underthe signals in the resulting mass spectra are proportional toconcentration (when normalized and corrected for background). Methodsfor preparing and using such chips are described in U.S. Pat. No.6,024,925, co-pending U.S. application Ser. Nos. 08/786,988, 09/364,774,09/371,150 and 09/297,575; see, also U.S. application Ser. No.PCT/US97/20195, which published as WO 98/20020. Chips and kits forperforming these analyses are commercially available from SEQUENOM underthe trademark MassARRAY. MassArray relies on the fidelity of theenzymatic primer extension reactions combined with the miniaturizedarray and MALDI-TOF (Matrix-Assisted Laser Desorption Ionization-Time ofFlight) mass spectrometry to deliver results rapidly. It accuratelydistinguishes single base changes in the size of DNA fragmentsassociated with genetic variants without tags.

[0170] The methods provided herein permit quantitative determination ofalleles. The areas under the signals in the mass spectra can be used forquantitative determinations. The frequency is determined from the ratioof the signal to the total area of all of the spectrum and corrected forbackground. This is possible because of the PROBE technology asdescribed in the above applications incorporated by reference herein.

[0171] Additional methods of analyzing nucleic acids includeamplification-based methods including polymerase chain reaction (PCR),ligase chain reaction (LCR), mini-PCR, rolling circle amplification,autocatalytic methods, such as those using Qβ replicase, TAS, 3SR, andany other suitable method known to those of skill in the art.

[0172] Other methods for analysis and identification and detection ofpolymorphisms, include but are not limited to, allele specific probes,Southern analyses, and other such analyses.

[0173] The methods described below provide ways to fragment givenamplified or non-amplified nucleotide sequences thereby producing a setof mass signals when mass spectrometry is used to analyze the fragmentmixtures.

[0174] Amplified fragments are yielded by standard polymerase chainmethods (U.S. Pat. Nos. 4,683,195 and 4,683,202). The fragmentationmethod involves the use of enzymes that cleave single or double strandsof DNA and enzymes that ligate DNA. The cleavage enzymes can beglycosylases, nickases, and site-specific and non site-specificnucleases, such as, but are not limited to, glycosylases, nickases andsite-specific nucleases.

[0175] Glycosylase Fragmentation Method

[0176] DNA glycosylases specifically remove a certain type of nucleobasefrom a given DNA fragment. These enzymes can thereby produce abasicsites, which can be recognized either by another cleavage enzyme,cleaving the exposed phosphate backbone specifically at the abasic siteand producing a set of nucleobase specific fragments indicative of thesequence, or by chemical means, such as alkaline solutions and or heat.The use of one combination of a DNA glycosylase and its targetednucleotide would be sufficient to generate a base specific signaturepattern of any given target region.

[0177] Numerous DNA gicosylases are known, For example, a DNAglycosylase can be uracil-DNA glycolsylase (UDG) , 3-methyladenine DNAglycosylase, 3-methyladenine DNA glycosylase II, pyrimidine hydrate-DNAglycosylase, FaPy-DNA glycosylase, thymine mismatch-DNA glycosylase,hypoxanthine-DNA glycosylase, 5-Hydroxymethyluracil DNA glycosylase(HmUDG), 5-Hydroxymethylcytosine DNA glycosylase, or 1,N6-etheno-adenineDNA glycosylase (see, e.g.,, U.S. Pat. Nos. 5,536,649, 5,888, 795,5,952,176 and 6,099,553, International PCT application Nos. WO 97/03210,WO 99/54501; see, also, Eftedal et al. (1993) Nucleic Acids Res21:2095-2101, Bjelland and Seeberg (1987) Nucleic Acids Res.15:2787-2801, Saparbaev et al. (1995) Nucleic Acids Res. 23:3750-3755,Bessho (1999) Nucleic Acids Res. 27:979-983) corresponding to theenzyme's modified nucleotide or nucleotide analog target. uracil-DNAglycolsylase (UDG) is an exemplary glycosylase.

[0178] Uracil, for example, can be incorporated into an amplified DNAmolecule by amplifying the DNA in the presence of normal DNA precursornucleotides (e.g. dCTP, dATP, and dGTP) and dUTP. When the amplifiedproduct is treated with UDG, uracil residues are cleaved. Subsequentchemical treatment of the products from the UDG reaction results in thecleavage of the phosphate backbone and the generation of nucleobasespecific fragments. Moreover, the separation of the complementarystrands of the amplified product prior to glycosylase treatment allowscomplementary patterns of fragmentation to be generated. Thus, the useof dUTP and Uracil DNA glycosylase allows the generation of T specificfragments for the complementary strands, thus providing information onthe T as well as the A positions within a given sequence. Similar tothis, a C-specific reaction on both (complementary) strands (i.e. with aC-specific glycosylase) yields information on C as well as G positionswithin a given sequence if the fragmentation patterns of bothamplification strands are analyzed separately. Thus, with theglycosylase method and mass spectrometry, a full series of A, C, G and Tspecific fragmentation patterns can be analyzed.

[0179] Nickase Fragmentation Method

[0180] A DNA nickase, or DNase, can be used to recognize and cleave onestrand of a DNA duplex. Numerous nickases are known. Among these, forexample, are nickase NY2A nickase and NYS1 nickase (Megabase) with thefollowing cleavage sites:

[0181] NY2A: 5′ . . . R AG . . . 3′

[0182] 3′ . . . Y TC . . . 5′ where R=A or G and Y=C or T

[0183] NYS1: 5′ . . . CC[A/G/T] . . . 3′

[0184] 3′ . . . GG[T/C/A] . . . 5′.

[0185] Fen-Ligase Fragmentation Method

[0186] The Fen-ligase method involves two enzymes: Fen-1 enzyme and aligase. The Fen-1 enzyme is a site-specific nuclease known as a “flap”endonuclease (U.S. Pat. Nos. 5,843,669, 5,874,283, and 6,090,606). Thisenzyme recognizes and cleaves DNA “flaps” created by the overlap of twooligonucleotides hybridized to a target DNA strand. This cleavage ishighly specific and can recognize single base pair mutations, permittingdetection of a single homologue from an individual heterozygous at oneSNP of interest and then genotyping that homologue at other SNPsoccurring within the fragment. Fen-1 enzymes can be Fen-1 like nucleasese.g. human, murine, and Xenopus XPG enzymes and yeast RAD2 nucleases orFen-1 endonucleases from, for example, M. jannaschii, P. furiosus, andP. woesei. Among such enzymes are the Fen-1 enzymes.

[0187] The ligase enzyme forms a phosphodiester bond between two doublestranded nucleic acid fragments. The ligase can be DNA Ligase I or DNALigase IlIl (see, e.g., U.S. Pat. Nos. 5,506,137, 5,700,672, 5,858,705and 5,976,806; see, also, Waga, et al. (1994) J. Biol. Chem.269:10923-10934, Li et al. (1994) Nucleic Acids Res. 22:632-638, Arrandet al. (1986) J. Biol. Chem. 261:9079-9082, Lehman (1974) Science186:790-797, Higgins and Cozzarelli (1979) Methods Enzymol. 68:50-71,Lasko et al. (1990) Mutation Res. 236:277-287, and Lindahl and Barnes(1992) Ann. Rev. Biochem. 61:251-281 ). Thermostable ligase (EpicenterTechnologies), where “thermostable” denotes that the ligase retainsactivity even after exposure to temperatures necessary to separate twostrands of DNA, are among the ligases for use herein.

[0188] Type IIS Enzyme Fragmentation Method

[0189] Restriction enzymes bind specifically to and cleavedouble-stranded DNA at specific sites within or adjacent to a particularrecognition sequence. These enzymes have been classified into threegroups (e.g. Types I, II, and III) as known to those of skill in theart. Because of the properties of type I and type III enzymes, they havenot been widely used in molecular biological applications. Thus, forpurposes herein type II enzymes are among those contemplated. Of thethousands of restriction enzymes known in the art, there are 179different type II specificities. Of the 179 unique type II restrictionendonucleases, 31 have a 4-base recognition sequence, 11 have a 5-baserecognition sequence, 127 have a 6-base recognition sequence, and 10have recognition sequences of greater than six bases (U.S. Pat. No.5,604,098). Of category type II enzymes, type IIS is exemplified herein.

[0190] Type IIS enzymes can be Alw XI, Bbv I, Bce 83, Bpm I, Bsg I, BsmAI, Bsm FI, Bsa I, Bcc I, Bcg I, Ear I, Eco 57I, Esp 3I, Fau I, Fok I,Gsu I, Hga I, Mme I, Mbo II, Sap I, and the otheres.

[0191] The Fok I enzyme endonuclease is an exemplary well characterizedmember of the Type IIS class (see, e.g., U.S. Pat. Nos. 5,714,330,5,604,098, 5,436,150, 6,054,276 and 5,871,911; see, also, Szybalski etal. (1991 ) Gene 100:13-26, Wilson and Murray (1991) Ann. Rev. Genet.25:585-627, Sugisaki et al. (1981) Gene 16:73-78, Podhajska and Szalski(1985) Gene 40:175-182. Fok I recognizes the sequence 5′GGATG-3′ andcleaves DNA accordingly. Type IIS restriction sites can be introducedinto DNA targets by incorporating the sites into primers used to amplifysuch targets. Fragments produced by digestion with Fok I are sitespecific and can be analyzed by mass spectrometry methods such asMALDI-TOF mass spectrometry, ESI-TOF mass spectrometry, and any othertype of mass spectrometry well known to those of skill in the art.

[0192] Once a polymorphism has been found to correlate with a parametersuch as age, age groups can be screened for polymorphisms. Thepossibility of false results due to allelic dropout is examined by doingcomparative PCR in an adjacent region of the genome.

[0193] Analyses

[0194] In using the database, allelic frequencies can be determinedacross the population by analyzing each sample in the populationindividually, determining the presence or absence of allele or marker ofinterest in each individual sample, and then determining the frequencyof the marker in the population. The database can then be sorted(stratified) to identify any correlations between the allele and aselected parameter using standard statistical analysis. If a correlationis observed, such as a decrease in a particular marker with age orcorrelation with sex or other parameter, then the marker is a candidatefor further study, such as genetic mapping to identify a gene or pathwayin which it is involved. The marker can then be correlated, for example,with a disease. Haplotying also can be carried out. Genetic mapping canbe effected using standard methods and can also require use of databasesof others, such as databases previously determined to be associated witha disorder.

[0195] Exemplary analyses have been performed and these are shown in thefigures, and discussed herein.

[0196] Sample Pooling

[0197] It has been found that using the databases provided herein, orany other database of such information, substantially the samefrequencies that were obtained by examining each sample separately canbe obtained by pooling samples, such as in batches of 10, 20, 50, 100,200, 500, 1000 or any other number. A precise number can be determinedempirically if necessary, and can be as low as 3.

[0198] In one embodiment, the frequency of genotypic and other markerscan be obtained by pooling samples. To do this a target population and agenetic variation to be assessed is selected, a plurality of samples ofbiopolymers are obtained from members of the population, and thebiopolymer from which the marker or genotype can be inferred isdetermined or detected. A comparison of samples tested in pools andindividually and the sorted results therefrom are shown in FIG. 9, whichshows frequency of the factor VII Allele 353Q. FIG. 10 depicts thefrequency of the CETP Allele in pooled versus individual samples. FIG.15 shows ethnic diversity among various ethnic groups in the databaseusing pooled DNA samples to obtain the data. FIGS. 12-14 show massspectra for these samples.

[0199] Pooling of test samples has application not only to the healthydatabases provided herein, but also to use in gathering data for entryinto any database of subjects and genotypic information, includingtypical databases derived from diseased populations. What isdemonstrated herein, is the finding that the results achieved arestatistically the same as the results that would be achieved if eachsample is analyzed separately. Analysis of pooled samples by a method,such as the mass spectrometric methods provided herein, permitsresolution of such data and quantitation of the results.

[0200] For factor VII the R53Q acid polymorphism was assessed. In FIG.9, the “individual” data represent allelic frequency observed in 92individuals reactions. The pooled data represent the allelic frequencyof the same 92 individuals pooled into a single probe reaction. Theconcentration of DNA in the samples of individual donors is 250nanograms. The total concentration of DNA in the pooled samples is also250 nanograms, where the concentration of any individual DNA is 2.7nanograms.

[0201] It also was shown that it is possible to reduce the DNAconcentration of individuals in a pooled samples from 2.7 nanograms to0.27 nanograms without any change in the quality of the spectrum or theability to quantitate the amount of sample detected. Hence lowconcentrations of sample can be used in the pooling methods.

[0202] Use of the Databases and Markers Identified Thereby

[0203] The successful use of genomics requires a scientific hypothesis(i.e., common genetic variation, such as a SNP), a study design (i.e.,complex disorders), samples and technology, such as the chip-based massspectrometric analyses (see, e.g., U.S. Pat. No. 5,605,798, U.S. Pat.No. 5,777,324, U.S. Pat. No. 6,043,031, allowed copending U.S.application Ser. No. 08/744,481, U.S. application Ser. No. 08/990,851,International PCT application No. WO 98/20019, copending U.S.application Ser. No. 09/285,481, which describes an automated processline for analyses; see, also, U.S. application Ser. Nos. 08/617,256,09/287,681, 09/287,682, 09/287,141 and 09/287,679, allowed copendingU.S. application Ser. No. 08/744,481, International PCT application No.PCT/US97/20444, published as International PCT application No. WO98/20019, and based upon U.S. application Ser. Nos. 08/744,481,08/744,590, 08/746,036, 08/746,055, 08/786,988, 08/787,639, 08/933,792,08/746,055, 09/266,409, 08/786,988 and 08/787,639; see, also U.S.application Ser. No. 09/074,936). All of these aspects can be used inconjunction with the databases provided herein and samples in thecollection.

[0204] The databases and markers identified thereby can be used, forexample, for identification of previously unidentified or unknowngenetic markers and to identify new uses for known markers. As markersare identified, these can be entered into the database to use as sortingparameters from which additional correlations can be determined.

[0205] Previously Unidentified or Unknown Genetic Markers

[0206] The samples in the healthy databases can be used to identify newpolymorphisms and genetic markers, using any mapping, sequencing,amplification and other methodologies, and in looking for polymorphismsamong the population in the database. The thus-identified polymorphismcan then be entered into the database for each sample, and the databasesorted (stratified) using that polymorphism as a sorting parameter toidentify any patterns and correlations that emerge, such as agecorrelated changes in the frequency of the identified marker. If acorrelation is identified, the locus of the marker can be mapped and itsfunction or effect assessed or deduced.

[0207] Thus, the databases here provide means for:

[0208] identification of significantly different allelic frequencies ofgenetic factors by comparing the occurrence or disappearance of themarkers with increasing age in population and then associating themarkers with a disease or a biochemical pathway;

[0209] identification of significantly different allelic frequencies ofdisease causing genetic factors by comparing the male with the femalepopulation or comparing other selected stratified populations andassociating the markers with a disease or a biochemical pathway;

[0210] identification of significantly different allelic frequencies ofdisease causing genetic factors by comparing different ethnic groups andassociating the markers with a disease or a biochemical pathway that isknown to occur in high frequency in the ethnic group;

[0211] profiling potentially functional variants of genes through thegeneral panmixed population stratified according to age, sex, and ethnicorigin and thereby demonstrating the contribution of the variant genesto the physical condition of the investigated population;

[0212] identification of functionally relevant gene variants by genedisequilibrium analysis performed within the general panmixed populationstratified according to age, sex, and ethnic origin and therebydemonstrating their contribution to the physical condition ofinvestigated population;

[0213] identification of potentially functional variants of chromosomesor parts of chromosomes by linkage disequilibrium analysis performedwithin the general panmixed population stratified according to age, sex,and ethnic origin and thereby demonstrating their contribution to thephysical condition of investigated population.

[0214] Uses of the Identified Markers and Known Markers

[0215] The databases can also be used in conjunction with known markersand sorted to identify any correlations. For example, the databases canbe used for:

[0216] determination and evaluation of the penetrance of medicallyrelevant polymorphic markers;

[0217] determination and evaluation of the diagnostic specificity ofmedically relevant genetic factors;

[0218] determination and evaluation of the positive predictive value ofmedically relevant genetic factors;

[0219] determination and evaluation of the onset of complex diseases,such as, but are not limited to, diabetes, hypertension, autoimmunediseases, arteriosclerosis, cancer and other diseases within the generalpopulation with respect to their causative genetic factors;

[0220] delineation of the appropriate strategies for preventive diseasetreatment;

[0221] delineation of appropriate timelines for primary diseaseintervention;

[0222] validation of medically relevant genetic factors identified inisolated populations regarding their general applicability;

[0223] validation of disease pathways including all potential targetstructures identified in isolated populations regarding their generalapplicability; and

[0224] validation of appropriate drug targets identified in isolatedpopulations regarding their general applicability.

[0225] Among the diseases and disorders for which polymorphisms can belinked include, those linked to inborn errors of metabolism, acquiredmetabolic disorders, intermediary metabolism, oncogenesis pathways,blood clotting pathways, and DNA synthetic and repair pathways, DNArepair/replication/transcription factors and activities, e.g., such asgenes related to oncogenesis, aging and genes involved in blood clottingand the related biochemical pathways that are related to thrombosis,embolism, stroke, myocardial infarction, angiogenesis and oncogenesis.

[0226] For example, a number of diseases are caused by or involvedeficient or defective enzymes in intermediary metabolism (see, e.q.,Tables 1 and 2, below) that result, upon ingestion of the enzymesubstrates, in accumulation of harmful metabolites that damage organsand tissues, particularly an infant's developing brain and other organs,resulting in mental retardation and other developmental disorders.

[0227] Identification of Markers and Genes for Such Disorders is ofGreat Interest.

[0228] Model Systems

[0229] Several gene systems, p21, p53 and Lipoprotein Lipasepolymorphism (N291S), were selected. The p53 gene is a tumor suppressorgene that is mutated in diverse tumor types. One common allelic variantoccurs at codon 72. A polymorphism that has been identified in the p53gene, i.e., the R72P allele, results in an amino acid exchange, arginineto proline, at codon 72 of the gene.

[0230] Using diseased populations, it has been shown that there areethnic differences in the allelic distribution of these alleles amongAfrican-Americans and Caucasians in the U.S. The results here supportthis finding and also demonstrate that the results obtained with ahealthy database are meaningful (see, FIG. 7B).

[0231] The 291S allele leads to reduced levels of high densitylipoprotein cholesterol (HDL-C) that is associated with an increasedrisk of males for arteriosclerosis and in particular myocardialinfarction (see, Reymer et al. (1995) Nature Genetics 10:28-34).

[0232] Both genetic polymorphisms were profiled within a part of theCaucasian population-based sample bank. For the polymorphism located inthe lipoprotein lipase gene a total of 1025 unselected individuals (436males and 589 females) were tested. Genomic DNA was isolated from bloodsamples obtained from the individuals.

[0233] As shown in the Examples and figures, an exemplary databasecontaining about 5000 subjects, answers to the questionnaire (see FIG.3), and genotypic information has been stratified. A particular knownallele has been selected, and the samples tested for the marker usingmass spectrometric analyses, particularly PROBE (see the EXAMPLES) toidentify polymorphisms in each sample. The population in the databasehas been sorted according to various parameters and correlations havebeen observed. For example, FIGS. 2A-C, show sorting of the data by ageand sex for the Lipoprotein Lipase gene in the Caucasian population inthe database. The results show a decrease in the frequency of the allelewith age in males but no such decrease in females. Other alleles thathave been tested against the database, include, alleles of p53, p21 andfactor VII. Results when sorted by age are shown in the figures.

[0234] These examples demonstrate an effect of altered frequency ofdisease causing genetic factors within the general population. Thescientific interpretation of those results allows prediction of medicalrelevance of polymorphic genetic alterations. In addition, conclusionscan be drawn with regard to their penetrance, diagnostic specificity,positive predictive value, onset of disease, most appropriate onset ofpreventive strategies, and the general applicability of geneticalterations identified in isolated populations to panmixed populations.

[0235] Therefore, an age- and sex-stratified population-based samplebank that is ethnically homogenous is a suitable tool for rapididentification and validation of genetic factors regarding theirpotential medical utility.

[0236] Exemplary Computer System for Creating, Storing and Processingthe Databases

[0237] Systems

[0238] Systems, including computers, containing the databases areprovided herein. The computers and databases can be used in conjunction,for example, with the APL system (see, copending U.S. application Ser.No. 09/285,481), which is an automated system for analyzing biopolymers,particularly nucleic acids. Results from the APL system can be enteredinto the database.

[0239] Any suitable computer system can be used. The computer system canbe integrated into systems for sample analysis, such as the automatedprocess line described herein (see, e.g., copending U.S. applicationSer. No. 09/285,481).

[0240]FIG. 17 is a block diagram of a computer constructed to provideand process the databases described herein. The processing thatmaintains the database and performs the methods and procedures can beperformed on multiple computers all having a similar construction, orcan be performed by a single, integrated computer. For example, thecomputer through which data are added to the database can be separatefrom the computer through which the database is sorted, or can beintegrated with it. In either arrangement, the computers performing theprocessing can have a construction as illustrated in FIG. 17.

[0241]FIG. 17 is a block diagram of an exemplary computer 1700 thatmaintains the database described above and performs the methods andprocedures. Each computer 1700 operates under control of a centralprocessor unit (CPU) 1702, such as a “Pentium” microprocessor andassociated integrated circuit chips, available from Intel Corporation ofSanta Clara, Calif., USA. A computer user can input commands and datafrom a keyboard and display mouse 1704 and can view inputs and computeroutput at a display 1706. The display is typically a video monitor orflat panel display device. The computer 1700 also includes a directaccess storage device (DASD) 1707, such as a fixed hard disk drive. Thememory 1708 typically comprises volatile semiconductor random accessmemory (RAM). Each computer can include a program product reader 1710that accepts a program product storage device 1712, from which theprogram product reader can read data (and to which it can optionallywrite data). The program product reader can comprise, for example, adisk drive, and the program product storage device can compriseremovable storage media such as a magnetic floppy disk, an opticalCD-ROM disc, a CD-R disc, a CD-RW disc, or a DVD data disc. If desired,the computers can be connected so they can communicate with each other,and with other connected computers, over a network 1713. Each computer1700 can communicate with the other connected computers over the network1713 through a network interface 1714 that enables communication over aconnection 1716 between the network and the computer.

[0242] The computer 1700 operates under control of programming stepsthat are temporarily stored in the memory 1708 in accordance withconventional computer construction. When the programming steps areexecuted by the CPU 1702, the pertinent system components perform theirrespective functions. Thus, the programming steps implement thefunctionality of the system as described above. The programming stepscan be received from the DASD 1707, through the program product reader1712, or through the network connection 1716. The storage drive 1710 canreceive a program product, read programming steps recorded thereon andtransfer the programming steps into the memory 1708 for execution by theCPU 1702. As noted above, the program product storage device 1710 cancomprise any one of multiple removable media having recordedcomputer-readable instructions, including magnetic floppy disks andCD-ROM storage discs. Other suitable program product storage devices caninclude magnetic tape and semiconductor memory chips. In this way, theprocessing steps necessary for operation can be embodied on a programproduct.

[0243] Alternatively, the program steps can be received into theoperating memory 1708 over the network 1713. In the network method, thecomputer receives data including program steps into the memory 1708through the network interface 1714 after network communication has beenestablished over the network connection 1716 by well-known methods thatwill be understood by those skilled in the art without furtherexplanation. The program steps are then executed by the CPU 1702 toimplement the processing of the Garment Database system.

[0244] It should be understood that all of the computers of the systemand can have a construction similar to that shown in FIG. 17. Detailsdescribed with respect to the FIG. 17 computer 1700 will be understoodto apply to all computers of the system 1700. This is indicated bymultiple computers 1700 shown connected to the network 1713. Any one ofthe computers 1700 can have an alternative construction, so long as theycan communicate with the other computers and support the functionalitydescribed herein.

[0245]FIG. 18 is a flow diagram that illustrates the processing stepsperformed using the computer illustrated in FIG. 17, to maintain andprovide access to the databases, such as for identifying polymorphicgenetic markers. In particular, the information contained in thedatabase is stored in computers having a construction similar to thatillustrated in FIG. 17. The first step for maintaining the database, asindicated in FIG. 18, is to identify healthy members of a population. Asnoted above, the population members are subjects that are selected onlyon the basis of being healthy, and where the subjects are mammals, suchas humans, they can be selected based upon apparent health and theabsence of detectable infections. The step of identifying is representedby the flow diagram box numbered 1802.

[0246] The next step, represented by the flow diagram box numbered 1804,is to obtain identifying and historical information and data relating tothe identified members of the population. The information and datacomprise parameters for each of the population members, such as memberage, ethnicity, sex, medical history, and ultimately genotypicinformation. Initially, the parameter information is obtained from aquestionnaire answered by each member, from whom a body tissue or bodyfluid sample also is obtained. The step of entering and storing theseparameters into the database of the computer is represented by the flowdiagram box numbered 1806. As additional information about eachpopulation member and corresponding sample is obtained, this informationcan be inputted into the database and can serve as a sorting parameter.

[0247] In the next step, represented by the flow diagram box numbered1808, the parameters of the members are associated with an indexer. Thisstep can be executed as part of the database storage operation, such aswhen a new data record is stored according to the relational databasestructure and is automatically linked with other records according tothat structure. The step 1806 also can be executed as part of aconventional data sorting or retrieval process, in which the databaseentries are searched according to an input search or indexing key valueto determine attributes of the data. For example, such search and sorttechniques can be used to follow the occurrence of known genetic markersand then determine if there is a correlation with diseases for whichthey have been implicated. Examples of this use are for assessing thefrequencies of the p53 and Lipoprotein Lipase polymorphisms.

[0248] Such searching of the database also can be valuable foridentifying one or more genetic markers whose frequency changes withinthe population as a function of age, ethnic group, sex, or some othercriteria. This can allow the identification of previously unknownpolymorphisms and, ultimately, identification of a gene or pathwayinvolved in the onset and progression of disease.

[0249] In addition, the database can be used for taking an identifiedpolymorphism and ascertaining whether it changes in frequency when thedata are sorted according to a selected parameter.

[0250] In this way, the databases and methods provided herein permit,among other things, identification of components, particularly keycomponents, of a disease process by understanding its geneticunderpinnings, and also an understanding of processes, such asindividual drug responses. The databases and methods provided hereinalso can be used in methods involving elucidation of pathologicalpathways, in developing new diagnostic assays, identifying new potentialdrug targets, and in identifying new drug candidates.

[0251] Morbidity and/or Early Mortality Associated Polymorphisms

[0252] A database containing information provided by a population ofhealthy blood donors who were not selected for any particular disease tocan be used to identify polymorphisms and the alleles in which they arepresent, whose frequency decreases with age. These can representmorbidity susceptibility markers and genes.

[0253] Polymorphisms of the genome can lead to altered gene function,protein function or genome instability. To identify those polymorphismswhich have a clinical relevance/utility is the goal of a world-widescientific effort. It can be expected that the discovery of suchpolymorphisms will have a fundamental impact on the identification anddevelopment of novel drug compounds to cure diseases. The strategy toidentify valuable polymorphisms is cumbersome and dependent upon theavailability of many large patient and control cohorts to show diseaseassociation. In particular, genes that cause a general risk of thepopulation to suffer from any disease (morbidity susceptibility genes)will escape these case/control studies entirely.

[0254] Here described is a screening strategy to identify morbiditysusceptibility genes underlying a variety of different diseases. Thedefinition of a morbidity susceptibility gene is a gene that isexpressed in many different cell types or tissues (housekeeping gene)and its altered function can facilitate the expression of a clinicalphenotype caused by disease-specific susceptibility genes that areinvolved in a pathway specific for this disorder. In other words, thesemorbidity susceptibility genes predispose people to develop a distinctdisease according to their genetic make-up for this disease.

[0255] Candidates for morbidity susceptibility genes can be found at thebottom level of pathways involving transcription, translation,heat-shock proteins, protein trafficking, DNA repair, assembly systemsfor subcellular structures (e.g. mitochondria, peroxysomes and othercellular microbodies), receptor signaling cascades, immunology, etc.Those pathways control the quality of life at the cellular level as wellas for the entire organism. Mutations/polymorphisms located in genesencoding proteins for those pathways can reduce the fitness of cells andmake the organism more susceptible to express the clinical phenotypecaused by the action of a disease-specific susceptibility gene.Therefore, these morbidity susceptibility genes can be potentiallyinvolved in a whole variety of different complex diseases if not in all.Disease-specific susceptibility genes are involved in pathways that canbe considered as disease-specific pathways like glucose-, lipid, hormonemetabolism, etc.

[0256] The exemplified method permit, among other things, identificationof genes and/or gene products involved in a man's general susceptibilityto morbidity and/or mortality; use of these genes and/or gene productsin studies to elucidate the genetic underpinnings of human diseases; useof these genes and/or gene products in combinatorial statisticalanalyses without or together with disease-specific susceptibility genes;use of these genes and/or gene products to predict penetrance of diseasesusceptibility genes; use of these genes and/or gene products inpredisposition and/or acute medical diagnostics and use of these genesand/or gene products to develop drugs to cure diseases and/or to extendthe life span of humans.

[0257] Screening Process

[0258] The healthy population stratified by age, gender and ethnicity,etc. is a very efficient and a universal screening tool for morbidityassociated genes. Changes of allelic frequencies in the young comparedto the old population are expected to indicate putative morbiditysusceptibility genes. Individual samples of this healthy population basecan be pooled to further increase the throughput. In an experiment,pools of young and old Caucasian females and males were applied toscreen more than 400 randomly chosen single nucleotide polymorphismslocated in many different genes. Candidate polymorphisms were identifiedif the allelic difference was greater than 8% between young and old forboth or only one of the genders. The initial results were assayed againin at least one independent subsequent experiments. Repeated experimentsare necessary to recognize unstable biochemical reactions, which occurwith a frequency of about 2-3% and can mimic age-related allelicfrequency differences. Average frequency differences and standarddeviations are calculated after successful reproducibility of initialresults. The final allelic frequency is then compared to a referencepopulation of Caucasian CEPH sample pool. The result should show similarallelic frequencies in the young Caucasian population. Subsequently, theexact allele frequencies of candidates including genotype informationwere obtained by analyzing all individual samples. This procedure isstraight forward with regard to time and cost. It enables the screeningof an enormous number of SNPs. So far, several markers with a highlysignificant association to age were identified and described below.

[0259] In general at least 5 individuals in a stratified populationshould to be screened to produce statistically significant results. Thefrequency of the allele is determined for an age stratified population.Chi square analysis is then performed on the allelic frequencies todetermine if the difference between age groups is statisticallysignificant. A p value less than of 0.1 is considered to represent astatistically significant difference. Typically the p value should beless than 0.05.

[0260] Clinical Trials

[0261] The identification of markers whose frequency in a populationdecreases with age also allows for better designed and balanced clinicaltrials. Currently, if a clinical trial utilizes a marker as asignificant endpoint in a study and the marker disappears with age, thenthe results of the study can be inaccurate. By using methods providedherein, it can be ascertained that if a marker decreases in frequencywith age. This information can be considered and controlled whendesigning the study. For, example, an age independent marker could besubstituted in its place.

[0262] The following examples are included for illustrative purposesonly and are not intended to limit the scope of the invention.

EXAMPLE 1

[0263] This example describes the use of a database containinginformation provided by a population of healthy blood donors who werenot selected for any particular disease to determine the distribution ofallelic frequencies of known genetic markers with age and by sex in aCaucasian subpopulation of the database. The results described in thisexample demonstrate that a disease-related genetic marker orpolymorphism can be identified by sorting a healthy database by aparameter or parameters, such as age, sex and ethnicity.

[0264] Generating a Database

[0265] Blood was obtained by venous puncture from human subjects who metblood bank criteria for donating blood. The blood samples were preservedwith EDTA at pH 8.0 and labeled. Each donor provided information such asage, sex, ethnicity, medical history and family medical history. Eachsample was labeled with a barcode representing identifying information.A database was generated by entering, for each donor, the subjectidentifier and information corresponding to that subject into the memoryof a computer storage medium using commercially available software,e.g., Microsoft Access.

[0266] Model Genetic Markers

[0267] The frequencies of polymorphisms known to be associated at somelevel with disease were determined in a subpopulation of the subjectsrepresented in the database. These known polymorphisms occur in the p21,p53 and Lipoprotein Lipase genes. Specifically, the N291S polymorphism(N291S) of the Lipoprotein Lipase gene, which results in a substitutionof a serine for an asparagine at amino acid codon 291, leads to reducedlevels of high density lipoprotein cholesterol (HDL-C) that isassociated with an increased risk of males for arteriosclerosis and inparticular myocardial infarction (see, Reymer et al. (1995) NatureGenetics 10:28-34).

[0268] The p53 gene encodes a cell cycle control protein that assessesDNA damage and acts as a transcription factor regulating genes thatcontrol cell growth, DNA repair and apoptosis (programmed cell death).Mutations in the p53 gene have been found in a wide variety of differentcancers, including different types of leukemia, with varying frequency.The loss of normal p53 function results in genomic instability anuncontrolled cell growth. A polymorphism that has been identified in thep53 gene, i.e., the R72P allele, results in the substitution of aproline for an arginine at amino acid codon 72 of the gene.

[0269] The p21 gene encodes a cyclin-dependent kinase inhibitorassociated with G1phase arrest of normal cells. Expression of the p21gene triggers apoptosis. Polymorphisms of the p21 gene have beenassociated with Wilms' tumor, a pediatric kidney cancer. Onepolymorphism of the p21 gene, the S31R polymorphism, results in asubstitution of an arginine for a serine at amino acid codon 31.

[0270] Database Analysis

[0271] Sorting of Subjects According to Specific Parameters

[0272] The genetic polymorphisms were profiled within segments of theCaucasian subpopulation of the sample bank. For p53 profiling, thegenomic DNA isolated from blood from a total of 1277 Caucasian subjectsage 18-59 years and 457 Caucasian subjects age 60-79 years was analyzed.For p21 profiling, the genomic DNA isolated from blood from a total of910 Caucasian subjects age 18-49 years and 824 Caucasian subjects age50-79 years was analyzed. For lipoprotein lipase gene profiling, thegenomic DNA from a total of 1464 Caucasian females and 1470 Caucasianmales under 60 years of age and a total of 478 Caucasian females and 560Caucasian males over 60 years of age was analyzed.

[0273] Isolation and Analysis of Genomic DNA

[0274] Genomic DNA was isolated from blood samples obtained from theindividuals. Ten milliliters of whole blood from each individual wascentrifuged at 2000×g. One milliliter of the buffy coat was added to 9ml of 155 mM NH₄Cl, 10 mM KHCO₃, and 0.1 mM Na₂EDTA, incubated 10 min atroom temperature and centrifuged for 10 min at 2000×g. The supernatantwas removed, and the white cell pellet was washed in 155 mM NH₄Cl, 10 mMKHCO₃ and 0.1 mM Na₂EDTA and resuspended in 4.5 ml of 50 mM Tris, 5 mMEDTA and 1% SDS. Proteins were precipitated from the cell lysate by 6 mMammonium acetate, pH 7.3, and then separated from the nucleic acids bycentrifugation at 3000×g. The nucleic acid was recovered from thesupernatant by the addition of an equal volume of 100% isopropanol andcentrifugation at 2000×g. The dried nucleic acid pellet was hydrated in10 mM Tris, pH 7.6, and 1 mM Na₂EDTA and stored at 4° C.

[0275] Assays of the genomic DNA to determine the presence or absence ofthe known genetic markers were developed using the BiomassPROBE™detection method (primer oligo base extension) reaction. This methoduses a single detection primer followed by an oligonucleotide extensionstep to give products, which can be readily resolved by massspectrometry, and, in particular, MALDI-TOF mass spectrometry. Theproducts differ in length depending on the presence or absence of apolymorphism. In this method, a detection primer anneals adjacent to thesite of a variable nucleotide or sequence of nucleotides, and the primeris extended using a DNA polymerase in the presence of one or moredideoxyNTPs and, optionally, one or more deoxyNTPs. The resultingproducts are resolved by MALDI-TOF mass spectrometry. The mass of theproducts as measured by MALDI-TOF mass spectrometry makes possible thedetermination of the nucleotide(s) present at the variable site.

[0276] First, each of the Caucasian genomic DNA samples was subjected tonucleic acid amplification using primers corresponding to sites 5′ and3′ of the polymorphic sites of the p21 (S31R allele), p53 (R72P allele)and Lipoprotein Lipase (N291S allele) genes. One primer in each primerpair was biotinylated to permit immobilization of the amplificationproduct to a solid support. Specifically, the polymerase chain reactionprimers used for amplification of the relevant segments of the p21, p53and lipoprotein lipase genes are shown below: US4p21c31-2F (SEQ ID NO:9) and US5p21-2R (SEQ ID NO: 10) for p21 gene amplification;US4-p53-ex4-F (also shown as p53-ex4US4 (SEQ ID NO: 2)) and US5-p53/2-4R(also shown as US5P53/4R (SEQ ID NO: 3)) for p53 gene amplification; andUS4-LPL-F2 (SEQ ID NO: 16) and US5-LPL-R2 (SEQ ID NO: 17) forlipoprotein lipase gene amplification.

[0277] Amplification of the respective DNA sequences was conductedaccording to standard protocols. For example, primers can be used in aconcentration of 8 pmol. The reaction mixture (e.g., total volume 50 μl)can contain Taq-polymerase including 10×buffer and dTNPs. Cyclingconditions for polymerase chain reaction amplification can typically beinitially 5 min. at 95° C., followed by 1 min. at 94° C., 45 sec at 53°C., and 30 sec at 72° C. for 40 cycles with a final extension time of 5min at 72° C. Amplification products can be purified by using Qiagen'sPCR purification kit (No. 28106) according to manufacturer'sinstructions. The elution of the purified products from the column canbe done in 50 μl TE-buffer (10 mM Tris, 1 mM EDTA, pH 7.5).

[0278] The purified amplification products were immobilized via abiotin-avidin linkage to streptavidin-coated beads and thedouble-stranded DNA was denatured. A detection primer was then annealedto the immobilized DNA using conditions such as, for example, thefollowing: 50 μl annealing buffer (20 mM Tris, 10 mM KCl, 10 mM(NH₄)₂SO₄, 2 mM MgSO₂, 1% Triton X-100, pH 8) at 50° C. for 10 min,followed by washing of the beads three times with 200 μl washing buffer(40 mM Tris, 1 mM EDTA, 50 mM NaCl, 0.1% Tween 20, pH 8.8) and once in200 μl TE buffer.

[0279] The PROBE extension reaction was performed, for example, by usingsome components of the DNA sequencing kit from USB (No. 70770) and dNTPsor ddNTPs from Pharmacia. An exemplary protocol could include a totalreaction volume of 45 μl, containing of 21 μl water, 6 μlSequenase-buffer, 3 μl 10 mM DTT solution, 4.5 μp, 0.5 mM of threedNTPs, 4.5 μl, 2 mM the missing one ddNTP, 5.5 μl glycerol enzymedilution buffer, 0.25 μl Sequenase 2.0, and 0.25 pyrophosphatase. Thereaction can then by pipetted on ice and incubated for 15 min at roomtemperature and for 5 min at 37° C. The beads can be washed three timeswith 200 μl washing buffer and once with 60 μl of a 70 mM NH₄-Citratesolution.

[0280] The DNA was denatured to release the extended primers from theimmobilized template. Each of the resulting extension products wasseparately analyzed by MALDI-TOF mass spectrometry using3-hydroxypicolinic acid (3-HPA) as matrix and a UV laser.

[0281] Specifically, the primers used in the PROBE reactions are asshown below: P21/31-3 (SEQ ID NO: 12) for PROBE analysis of the p21polymorphic site; P53/72 (SEQ ID NO: 4) for PROBE analysis of the p53polymorphic site; and LPL-2 for PROBE analysis of the lipoprotein lipasegene polymorphic site. In the PROBE analysis of the p21 polymorphicsite, the extension reaction was performed using dideoxy-C. The productsresulting from the reaction conducted on a “wild-type” allele template(wherein codon 31 encodes a serine) and from the reaction conducted on apolymorphic S31R allele template (wherein codon 31 encodes an arginine)are shown below and designated as P21/31-3 Ser (wt) (SEQ ID NO: 13) andP21/31-3 Arg (SEQ ID NO: 14), respectively. The masses for each productas can be measured by MALDI-TOF mass spectrometry are also provided(i.e., 4900.2 Da for the wild-type product and 5213.4 Da for thepolymorphic product).

[0282] In the PROBE analysis of the p53 polymorphic site, the extensionreaction was performed using dideoxy-C. The products resulting from thereaction conducted on a “wild-type” allele template (wherein codon 72encodes an arginine) and from the reaction conducted on a polymorphicR72P allele template (wherein codon 72 encodes a proline) are shownbelow and designated as Cod72 G Arg (wt) and Cod72 C Pro, respectively.The masses for each product as can be measured by MALDI-TOF massspectrometry are also provided (i.e., 5734.8 Da for the wild-typeproduct and 5405.6 Da for the polymorphic product).

[0283] In the PROBE analysis of the lipoprotein lipase gene polymorphicsite, the extension reaction was performed using a mixture of ddA andddT. The products resulting from the reaction conducted on a “wild-type”allele template (wherein codon 291 encodes an asparagine) and from thereaction conducted on a polymorphic N291S allele template (wherein codon291 encodes a serine) are shown below and designated as 291Asn and291Ser, respectively. The masses for each product as can be measured byMALDI-TOF mass spectrometry are also provided (i.e., 6438.2 Da for thewild-type product and 6758.4 Da for the polymorphic product).

[0284] P53-1 (R72P) PCR Product length: 407 bp                                        US4-p53-ex4-F                                        ctg aggacctggt cctctgactg (SEQID NO: 1) ctcttttcac ccatctacag tcccccttgc cgtcccaagc aatggatgatttgatgctgt ccccggacga tattgaacaa tggttcactg aagacccagg tccagatgaagctcccagaa  P53/72              72R tgccagaggc tgctccccgc gtggcccctgcaccagcagc tcctacaccg gcggcccctg                    c 72P caccagccccctcctggccc ctgtcatctt ctgtcccttc ccagaaaacc taccagggca gctacggtttccgtctgggc ttcttgcatt ctgggacagc caagtctgtg acttgcacgg tcagttgccctgaggggctg gcttccatga gacttcaa                              US5-p53/2-4RPrimers (SEQ ID NOs: 2-4) p53-ex4FUS4 ccc agt cac gac gtt gta aaa cgctga gga cct ggt cct ctg ac US5P53/4R agc gga taa caa ttt cac aca ggt tgaagt ctc atg gaa gcc P53/72 gcc aga ggc tgc tcc cc

[0285] Masses Product Termination: Allele ddC SEQ # Length Mass P53/72gccagaggctgctcccc 5 17 5132.4 Cod72 G Arg gccagaggctgctccccgc 6 195734.8 (wt) Cod72 C Pro gccagaggctgctccccc 7 18 5405.6

[0286] Biotinylated US5 primer is used in the PCR amplification.

[0287] LPL-1 (N291S)

[0288] Amino acid exchange asparagine to serine at codon 291 of thelipoprotein lipase gene. PCR Product length: 251 bp US4-LPL-F2 (SEQ IDNO: 16) gcgctccatt catctcttca tcgactctct gttgaatgaa gaaaatccaagtaaggccta (SEQ ID NO: 15) caggtgcagt tccaaggaag cctttgagaa agggctctgcttgagttgta gaaagaaccg             LPL-2             291N ctgcaacaatctgggctatg agatcaataa agtcagagcc aaaagaagca gcaaaatgta                            g 291S cctgaagact cgttctcaga tgccc                US4-LPL-R2 Primers (SEQ ID NOs: 16-18): US4-LPL-F2 cccagt cac gac gtt gta aaa cgg cgc tcc att cat ctc ttc US5-LPL-R2 agc ggataa caa ttt cac aca ggg ggc atc tga gaa cga gtc LPL-2 caa tct ggg ctatga gat ca

[0289] Masses Allele Product Termination: ddA, ddT SEQ # Length MassLPL-2 caatctgggctatgagatca 19 20 6141 291 Asn caatctgggctatgagatcaa 2021 6438.2 291 Ser caatctgggctatgagatcagt 21 22 6758.4

[0290] Biotinylated US5 primer is used in the PCR amplification. P21-1(S31R) Amino acid exchange serine to arginine at codon 31 of the tumorsuppressor gene p21. Product length: 207 bp US4p21c3l-2F                                         gtcc gtcagaaccc atgcggcagc (SEQID NO: 8)                                        p21/31-3 31S aaggcctgccgccgcctctt cggcccagtg gacagcgagc agctgagccg cgactgtgat                                                   a 31R gcgctaatggcgggctgcat ccaggaggcc cgtgagcgat ggaacttcga ctttgtcacc gagacaccactggaggg          US5p21-2R Primers (SEQ ID NOs: 9-11) US4p21c31-2F cccagt cac gac gtt gta aaa cgg tcc gtc aga acc cat gcg g US5p21-2R agc ggataa caa ttt cac aca ggc tcc agt ggt gtc tcg gtg ac P21/31-3 cag cga gcagct gag

[0291] Masses Allele Product Termination: ddC SEQ # Length Mass P21/31-3cagcgagcagctgag 12 15 4627 P21/31-3 Ser cagcgagcagctgagc 13 16 4900.2(wt) P21/31-3 Arg cagcgagcagctgagac 14 17 5213.4

[0292] Biotinylated US5 primer is used in the PCR amplification.

[0293] Each of the Caucasian subject DNA samples was individuallyanalyzed by MALDI-TOF mass spectrometry to determine the identity of thenucleotide at the polymorphic sites. The genotypic results of each assaycan be entered into the database. The results were then sorted accordingto age and/or sex to determine the distribution of allelic frequenciesby age and/or sex. As depicted in the Figures showing histograms of theresults, in each case, there was a differential distribution of theallelic frequencies of the genetic markers for the p21, p53 andlipoprotein lipase gene polymorphisms.

[0294]FIG. 8 shows the results of the p21 genetic marker assays andreveals a statistically significant decrease (from 13.3% to 9.2%) in thefrequency of the heterozygous genotype (S31 R) in Caucasians with age(18-49 years of age compared to 50-79 years of age). The frequencies ofthe homozygous (S31 and R31) genotypes for the two age groups are alsoshown, as are the overall frequencies of the S31 and R31 alleles in thetwo age groups (designated as *S31 and *R31, respectively in theFigure).

[0295] FIGS. 7A-C show the results of the p53 genetic marker assays andreveals a statistically significant decrease (from 6.7% to 3.7%) in thefrequency of the homozygous polymorphic genotype (P72) in Caucasianswith age (18-59 years of age compared to 60-79 years of age). Thefrequencies of the homozygous “wild-type” genotype (R72) and theheterozygous genotype (R72P) for the two age groups are also shown, asare the overall frequencies of the R72 and P72 alleles in the two agegroups (designated as *R72 and *P72, respectively in the Figure). Theseresults are consistent with the observation that allele is not benign,as p53 regulates expression of a second protein, p21, which inhibitscyclin-dependent kinases (CDKs) needed to drive cells through thecell-cycle (a mutation in either gene can disrupt the cell cycle leadingto increased cell division).

[0296]FIG. 2C shows the results of the lipoprotein lipase gene geneticmarker assays and reveals a statistically significant decrease (from1.97% to 0.54%) in the frequency of the polymorphic allele (S291) inCaucasian males with age (see also Reymer et al. (1995) Nature Genetics10:28-34). The frequencies of this allele in Caucasian females ofdifferent age groups are also shown.

EXAMPLE 2

[0297] This example describes the use of MALDI-TOF mass spectrometry toanalyze DNA samples of a number of subjects as individual samples and aspooled samples of multiple subjects to assess the presence or absence ofa polymorphic allele (the 353Q allele) of the Factor VII gene anddetermine the frequency of the allele in the group of subjects. Theresults of this study show that essentially the same allelic frequencycan be obtained by analyzing pooled DNA samples as by analyzing eachsample separately and thereby demonstrate the quantitative nature ofMALDI-TOF mass spectrometry in the analysis of nucleic acids.

[0298] Factor VII

[0299] Factor VII is a serine protease involved in the extrinsic bloodcoagulation cascade. This factor is activated by thrombin and works withtissue factor (Factor III) in the processing of Factor X to Factor Xa.There is evidence that supports an association between polymorphisms inthe Factor VII gene and increased Factor VII activity which can resultin an elevated risk of ischemic cardiovascular disease, includingmyocardial infarction. The polymorphism investigated in this study isR353Q (i.e., a substitution of a glutamic acid residue for an arginineresidue at codon 353 of the Factor VII gene) (see Table 5).

[0300] Analysis of DNA Samples for the Presence or Absence of the 353QAllele of the Factor VII Gene

[0301] Genomic DNA was isolated from separate blood samples obtainedfrom a large number of subjects divided into multiple groups of 92subjects per group. Each sample of genomic DNA was analyzed using theBiomassPROBE™ assay as described in Example 1 to determine the presenceor absence of the 353Q polymorphism of the Factor VII gene.

[0302] First, DNA from each sample was amplified in a polymerase chainreaction using primers F7-353FUS4 (SEQ ID NO: 24) and F7-353RUS5 (SEQ IDNO: 26) as shown below and using standard conditions, for example, asdescribed in Example 1. One of the primers was biotinylated to permitimmobilization of the amplification product to a solid support. Thepurified amplification products were immobilized via a biotin-avidinlinkage to streptavidin-coated beads and the double-stranded DNA wasdenatured. A detection primer was then annealed to the immobilized DNAusing conditions such as, for example, described in Example 1. Thedetection primer is shown as F7-353-P (SEQ ID NO: 27) below. The PROBEextension reaction was carried out using conditions, for example, suchas those described in Example 1. The reaction was performed using ddG.

[0303] The DNA was denatured to release the extended primers from theimmobilized template. Each of the resulting extension products wasseparately analyzed by MALDI-TOF mass spectrometry. A matrix such as3-hydroxypicolinic acid (3-HPA) and a UV laser could be used in theMALDI-TOF mass spectrometric analysis. The products resulting from thereaction conducted on a “wild-type” allele template (wherein codon 353encodes an arginine) and from the reaction conducted on a polymorphic353Q allele template (wherein codon 353 encodes a glutamic acid) areshown below and designated as 353 CGG and 353 CAG, respectively. Themasses for each product as can be measured by MALDI-TOF massspectrometry are also provided (i.e., 5646.8 Da for the wild-typeproduct and 5960 Da for the polymorphic product).

[0304] The MALDI-TOF mass spectrometric analyses of the PROBE reactionsof each DNA sample were first conducted separately on each sample (250nanograms total concentration of DNA per analysis). The allelicfrequency of the 353Q polymorphism in the group of 92 subjects wascalculated based on the number of individual subjects in which it wasdetected.

[0305] Next, the samples from 92 subjects were pooled (250 nanogramstotal concentration of DNA in which the concentration of any individualDNA is 2.7 nanograms), and the pool of DNA was subjected to MALDI-TOFmass spectrometric analysis. The area under the signal corresponding tothe mass of the 353Q polymorphism PROBE extension product in theresulting spectrum was integrated in order to quantitate the amount ofDNA present. The ratio of this amount to total DNA was used to determinethe allelic frequency of the 353Q polymorphism in the group of subjects.This type of individual sample vs. pooled sample analysis was repeatedfor numerous different groups of 92 different samples.

[0306] The frequencies calculated based on individual MALDI-TOF massspectrometric analysis of the 92 separate samples of each group of 92are compared to those calculated based on MALDI-TOF mass spectrometricanalysis of pools of DNA from 92 samples in FIG. 9. These comparisonsare shown as “pairs” of bar graphs in the Figure, each pair beinglabeled as a separate “pool” number, e.g., P1, P16, P2, etc. Thus, forexample, for P1, the allelic frequency of the polymorphism calculated byseparate analysis of each of the 92 samples was 11.41%, and thefrequency calculated by analysis of a pool of all of the 92 DNA sampleswas 12.09%.

[0307] The similarity in frequencies calculated by analyzing separateDNA samples individually and by pooling the DNA samples demonstratesthat it is possible, through the quantitative nature of MALDI-TOF massspectrometry, to analyze pooled samples and obtain accurate frequencydeterminations. The ability to analyze pooled DNA samples significantlyreduces the time and costs involved in the use of the non-selected,healthy databases as described herein. It has also been shown that it ispossible to decrease the DNA concentration of the individual samples ina pooled mixture from 2.7 nanograms to 0.27 nanograms without any changein the quality of the spectrum or the ability to quantitate the amountof sample detected.

[0308] Factor VII R353Q PROBE Assay

[0309] PROBE Assay for cod353 CGG>CAG (Arg>Gln), Exon 9 G>A. PCRfragment: 134 bp (incl. US tags; SEQ ID Nos. 22 and 23) Frequency of Aallele: Europeans about 0.1, Japanese/Chinese about 0.03-0.05 (Thromb.Haemost. 1995, 73:617-22; Diabetologia 1998, 41:760-6):              F7-353FUS4> 1201 GTGCCGGCTA CTCGGATGGC AGCAAGGACTCCTGCAAGGG GGACAGTGGA GGCCCACATG     F7-353-P>      A           <F7-353RUS5 1261 CCACCCACTA CCGGGGCACGTGGTACCTGA CGGGCATCGT CAGCTGGGGC CAGGGCTGCG Primers (SEQ ID NOs: 24-26)Tm^(gs) F7-353FUS4 CCC AGT CAC GAC GTT GTA AAA CGA TGG CAG CAA GGA CTCCTG 64° C. F7-353-P CAC ATG CCA CCC ACT ACC F7-353RUS5 AGC GGA TAA CAATTT CAC ACA GGT GAC GAT GCC CGT CAG GTA C 64° C.

[0310] Masses Allele Product Termination: ddG SEQ # Length Mass F7-353-Patgccacccactacc 27 18 5333.6 353 CGG cacatgccacccactaccg 28 19 5646.8353 CAG cacatgccacccactaccag 29 20 5960 US5-bio bio-agcggataacaatttcacacagg 30 23 7648.6

[0311] Conclusion

[0312] The above examples demonstrate an effect of altered frequency ofdisease causing genetic factors within the general population.Interpretation of those results allows prediction of the medicalrelevance of polymorphic genetic alterations. In addition, conclusionscan be drawn with regard to their penetrance, diagnostic specificity,positive predictive value, onset of disease, most appropriate onset ofpreventive strategies, and the general applicability of geneticalterations identified in isolated populations to panmixed populations.Therefore, an age- and sex-stratified population-based sample bank thatis ethnically homogenous is a suitable tool for rapid identification andvalidation of genetic factors regarding their potential medical utility.

EXAMPLE 3

[0313] Morbidity and Mortality Markers

[0314] Sample Band and Initial Screening

[0315] Healthy samples were obtained through the blood bank of SanBernardino, Calif. Donors signed prior to the blood collection a consentform and agreed that their blood will be used in genetic studies withregard to human aging. All samples were anomymized. Tracking back ofsamples is not possible.

[0316] Isolation of DNA from Blood Samples of a Healthy Donor Population

[0317] Blood is obtained from a donor by venous puncture and preservedwith 1 mM EDTA pH 8.0. Ten milliliters of whole blood from each donorwas centrifuged at 2000×g. One milliliter of the buffy coat was added to9 milliters of 155 mM NH₄Cl, 1 OmM KHCO₃, and 0.1 mM Na₂EDTA, incubated10 minutes at room temperature and centrifuged for 10 minutes at 2000×g.The supernatant was removed, and the white cell pellet was washed in 155mM NH₄Cl, 10 mM KHCO₃, and 0.1 mM Na₂EDTA and resuspended in 4.5milliliters of 50 mM Tris, 5 mM EDTA, and 1% SDS. Proteins wereprecipitated from the cell lysate by 6M Ammonium Acetate, pH 7.3, andseparated from the nucleic acid by centrifugation 3000×g. The nucleicacid was recovered from the supernatant by the addition of an equalvolume of 100% isopropanol and centrifugation at 2000×g. The driednucleic acid pellet was hydrated in lOmM Tris pH 7.6 and 1 mM Na2EDTAand stored at 4C.

[0318] In this study, samples were pooled as shown in Table 1. Bothparents of the blood donors were of Caucasian origin. TABLE 1 Pool IDSex Age-range # individuals SP1 Female 18-39 years 276 SP2 Males 18-39years 276 SP3 Females 60-69 years 184 SP4 Males 60-79 years 368

[0319] More than 400 SNPs were tested using all four pools. After onetest run 34 assays were selected to be re-assayed at least once.Finally, 10 assays showed repeatedly differences in allele frequenciesof several percent and, therefore, fulfilled the criteria to be testedusing the individual samples. Average allele frequency and standarddeviation is tabulated in Table 2. TABLE 2 Assay ID SP1 SP1-STD SP2SP2-STD SP3 SP3-STD SP4 SP4-STD 47861 0.457 0.028 0.433 0.042 0.3840.034 0.380 0.015 47751 0.276 0.007 0.403 0.006 0.428 0.052 0.400 0.09748319 0.676 0.013 0.627 0.018 0.755 0.009 0.686 0.034 48070 0.581 0.0340.617 0.045 0.561 n.a. 0.539 0.032 49807 0.504 0.034 0.422 0.020 0.4770.030 0.556 0.005 49534 0.537 0.017 0.503 n.a. 0.623 0.023 0.535 0.00949733 0.560 0.006 0.527 0.059 0.546 0.032 0.436 0.016 49947 0.754 0.0080.763 0.047 0.736 0.052 0.689 0.025 50128 0.401 0.022 0.363 0.001 0.2940.059 0.345 0.013 63306 0.697 0.012 0.674 0.013 0.712 0.017 0.719 0.005

[0320] So far, 7 out of the 10 potential morbidity markers were fullyanalyzed. Additional information about genes in which these SNPs arelocated was gathered through publicly available databases, includingGenbank.

[0321] AKAPS

[0322] Candidate morbidity and mortality markers include housekeepinggenes, such as genes involved in signal transduction. Among such genesare the A-kinase anchoring proteins (AKAPs) genes, which participate insignal transduction pathways involving protein phosphorylation. Proteinphosphorylation is an important mechanism for enzyme regulation and thetransduction of extracellular signals across the cell membrane ineukaryotic cells. A wide variety of cellular substrates, includingenzymes, membrane receptors, ion channels and transcription factors, canbe phosphorylated in response to extracellular signals that interactwith cells. A key enzyme in the phosphorylation of cellular proteins inresponse to hormones and neurotransmitters is cyclic AMP(cAMP)-dependent protein kinase (PKA). Upon activation by cAMP, PKA thusmediates a variety of cellular responses to such extracellular signals.An array of PKA isozymes are expressed in mammalian cells. The PKAsusually exist as inactive tetramers containing a regulatory (R) subunitdimer and two catalytic (C) subunits. Genes encoding three C subunits(Cα, Cβ and Cy) and four R subunits (RIα, RIβ, RIIα and RIIβ) have beenidentified [see Takio et al. (1982) Proc. Natl. Acad. Sci. U.S. A.79:2544-2548; Lee et al. (1983) Proc. Natl. Acad. Sci. U.S. A.80:3608-3612; Jahnsen et al. (1996) J. Biol. Chem. 261:12352-12361;Clegg et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85:3703-3707; andScott (1991) Pharmacol. Ther. 50:123-145]. The type I (RI) α and type II(RII) α subunits are distributed ubiquitously, whereas RIβ and RIIβ arepresent mainly in brain [see. e.g., Miki and Eddy (1999) J. Biol. Chem.274:29057-29062]. The type I PKA holoenzyme (RIα and RIβ) ispredominantly cytoplasmic, whereas the majority of type II PKA (RIIα andRIIβ) associates with cellular structures and organelles [Scott (1991)Pharmacol. Ther. 50:123-1451. Many hormones and other signals actthrough receptors to generate cAMP which binds to the R subunits of PKAand releases and activates the C subunits to phosphorylate proteins.Because protein kinases and their substrates are widely distributedthroughout cells, there are mechanisms in place in cells to localizeprotein kinase-mediated responses to different signals. One suchmechanism involves subcellular targeting of PKAs through associationwith anchoring proteins, referred to as A-kinase anchoring proteins(AKAPs), that place PKAs in close proximity to specific organelles orcytoskelet al components and particular substrates thereby providing formore specific PKA interactions and localized responses [see, e.g., Scottet al. (1990) J. Biol. Chem. 265:21561-21566; Bregman et al. (1991) J.Biol. Chem. 266:7207-7213; and Miki and Eddy (1999) J. Biol. Chem.274:29057-290621. Anchoring not only places the kinase close to thesubstrates, but also positions the PKA holoenzyme at sites where it canoptimally respond to fluctuations in the second messenger cAMP[Mochly-Rosen (1995) Science 268:247-251; Faux and Scott (1996) TrendsBiochem. Sci. 21:312-315; Hubbard and Cohen (1993) Trends Biochem. Sci.18:172-177].

[0323] Up to 75% of type II PKA is localized to various intracellularsites through association of the regulatory subunit (RII) with AKAPs[see, e.g., Hausken et al. (1996) J. Biol. Chem. 271:29016-290221. RIIsubunits of PKA bind to AKAPs with nanomolar affinity [Carr et al.(1992) J. Biol. Chem. 267:13376-13382], and many AKAP-RII complexes havebeen isolated from cell extracts. RI subunits of PKA bind to AKAPs withonly micromolar affinity [Burton et al. (1997) Proc. Natl. Acad. Sci.U.S.A. 94:11067-110721. Evidence of binding of a PKA RI subunit to anAKAP has been reported [Miki and Eddy (1998) J. Biol. Chem273:34384-34390] in which RIα-specific and RIα/RIIα dual specificity PKAanchoring domains were identified on FSC1/AKAP82. Additional dualspecific AKAPs, referred to as D-AKAP1 and D-AKAP2, which interact withthe type I and type II regulatory subunits of PKA have also beenreported [Huang et al. (1997) J. Biol. Chem. 272:8057-8064; Huang et al.(1997) Proc. Natl. Acad. Sci. U.S.A. 94:11184-11189].

[0324] More than 20 AKAPs have been reported in different tissues andspecies. Complementary DNAs (cDNAs) encoding AKAPs have been isolatedfrom diverse species, ranging from Caenorhabditis elegans andDrosophilia to human [see, e.g., Colledge and Scott (1999) Trends CellBiol. 9:216-2211. Regions within AKAPs that mediate association with RIIsubunits of PKA have been identified. These regions of approximately10-18 amino acid residues vary substantially in primary sequence, butsecondary structure predictions indicate that they are likely to form anamphipathic helix with hydrophobic residues aligned along one face ofthe helix and charged residues along the other [Carr et al. (1991) J.Biol. Chem. 266:14188-14192; Carr et al. (1992) J. Biol. Chem.267:13376-13382]. Hydrophobic amino acids with a long aliphatic sidechain, e.g., valine, leucine or isoleucine, can participate in bindingto RII subunits [Glantz et al. (1993) J. Biol. Chem. 268:12796-12804].

[0325] Many AKAPs also have the ability to bind to multiple proteins,including other signaling enzymes. For example, AKAP79 binds to PKA,protein kinase C (PKC) and the protein phosphatase calcineurin (PP2B)[Coghlan et al. (1995) Science 267:108-112 and Klauck et al. (1996)Science 271:1589-15921. Therefore, the targeting of AKAP79 to neuronalpostsynaptic membranes brings together enzymes with opposite catalyticactivities in a single complex.

[0326] AKAPs thus serve as potential regulatory mechanisms that increasethe selectivity and intensity of a cAMP-mediated response. There is aneed, therefore, to identify and elucidate the structural and functionalproperties of AKAPs in order to gain a complete understanding of theimportant role these proteins μplay in the basic functioning of cells.

[0327] AKAP10

[0328] The sequence of a human AKAP10 cDNA (also referred to as D-AKAP2)is available in the GenBank database, at accession numbers AF037439 (SEQID NO: 31) and NM 007202. The AKAP10 gene is located on chromosome 17.

[0329] The sequence of a mouse D-AKAP2 cDNA is also available in theGenBank database (see accession number AF021833). The mouse D-AKAP2protein contains an RGS domain near the amino terminus that ischaracteristic of proteins that interact with Gα subunits and possessGTPase activating protein-like activity [Huang et al. (1997) Proc. Natl.Acad. Sci. U.S.A. 94:11184-11189]. The human AKAP10 protein also hassequences homologous to RGS domains. The carboxy-terminal 40 residues ofthe mouse D-AKAP2 protein are responsible for the interaction with theregulatory subunits of PKA. This sequence is fairly well conservedbetween the mouse D-AKAP2 and human AKAP10 proteins.

[0330] Polymorphisms of the Human AKAP10 Gene and Polymorphic AKAP10Proteins

[0331] Polymorphisms of AKAP genes that alter gene expression,regulation, protein structure and/or protein function are more likely tohave a significant effect on the regulation of enzyme (particularly PKA)activity, cellular transduction of signals and responses thereto and onthe basic functioning of cells than polymorphisms that do not alter geneand/or protein function. Included in the polymorphic AKAPs providedherein are human AKAP10 proteins containing differing amino acidresidues at position number 646.

[0332] Amino acid 646 of the human AKAP10 protein is located in thecarboxy-terminal region of the protein within a segment thatparticipates in the binding of R-subunits of PKAs. This segment includesthe carboxy-terminal 40 amino acids.

[0333] The amino acid residue reported for position 646 of the humanAKAP10 protein is an isoleucine. Polymorphic human AKAP10 proteinsprovided herein have the amino acid sequence but contain residues otherthan isoleucine at amino acid position 646 of the protein. In particularembodiments of the polymorphic human AKAP10 proteins provided herein,the amino acid at position 646 is a valine, leucine or phenylalanineresidue.

[0334] An A to G Transition at Nucleotide 2073 of the Human AKAP10Coding Sequence

[0335] As described herein, an allele of the human AKAP10 gene thatcontains a specific polymorphism at position 2073 of the coding sequenceand thereby encodes a valine at position 646 has been detected invarying frequencies in DNA samples from younger and older segments ofthe human population. In this allele, the A at position 2073 of theAKAP10 gene coding sequence is changed from an A to a G, giving rise toan altered sequence in which the codon for amino acid 646 changes fromATT, coding for isoleucine, to GTT, coding for valine.

[0336] Morbidity Marker 1: Human Protein Kinase A Anchoring Protein(AKAP10-1)

[0337] PCR Amplification and BiomassPROBE assay detection of AKAP10-1 ina healthy donor population

[0338] PCR Amplification of Donor Population for AKAP 10

[0339] PCR primers were synthesized by OPERON using phosphoramiditechemistry. Amplification of the AKAP10 target sequence was carried outin single 50 μl PCR reaction with 100 ng-1 ug of pooled human genomicDNAs in a 50 μl PCR reaction. Individual DNA concentrations within thepooled samples were present in equal concentration with the finalconcentration ranging from 1-25 ng. Each reaction containing IX PCRbuffer (Qiagen, Valencia, Calif.), 200 uM dNTPs, 1U Hotstar Taqpolymerase (Qiagen, Valencia, Calif.), 4 mM MgCl₂, and 25 pmol of theforward primer containing the universal primer sequence and the targetspecific sequence 5′-TCTCAATCATGTGCATTGAGG-3′(SEQ ID NO: 45), 2 pmol ofthe reverse primer 5′-AGCGGATAACAATTTCACACAGGGATCACACAGCCATCAGCAG-3′(SEQ ID NO: 46), and 10 pmol of a biotinylated universal primercomplementary to the 5′ end of the PCR amplicon5′-AGCGGATAACAATTTCACACAGG-3′(SEQ ID NO: 47). After an initial round ofamplification with the target with the specific forward and reverseprimer, the 5′ biotinylated universal primer then hybridized and actedas a reverse primer thereby introducing a 3′ biotin capture moiety intothe molecule. The amplification protocol results in a 5′-biotinylateddouble stranded DNA amplicon and dramatically reduces the cost of highthroughput genotyping by eliminating the need to 5′ biotin label eachforward primer used in a genotyping. Thermal cycling was performed in0.2 mL tubes or 96 well plate using an MJ Research Thermal Cycler(calculated temperature) with the following cycling parameters: 94° C.for 5 min; 45 cycles: 94° C. for 20 sec, 56° C. for 30 sec, 72° C. for60 sec; 72° C. 3 min.

[0340] Immobilization of DNA

[0341] The 50 μl PCR reaction was added to 25 ul of streptavidin coatedmagnetic bead (Dynal) prewashed three times and resuspended in 1M NH₄Cl,0.06M NH₄OH. The PCR amplicons were allowed to bind to the beads for 15minutes at room temperature. The beads were then collected with a magnetand the supernatant containing unbound DNA was removed. The unboundstrand was released from the double stranded amplicons by incubation in100 mM NaOH and washing of the beads three times with 10 mM Tris pH 8.0.

[0342] BiomassPROBE Assay Analysis of Donor Population for AKAP10-1(clone 48319)

[0343] Genotyping using the BiomassPROBE assay methods was carried outby resuspending the DNA coated magnetic beads in 26 mM Tris-HCl pH 9.5,6.5 mM MgCl₂ and 50 mM each of dTTP and 50 mM each of ddCTP, ddATP,ddGTP, 2.5U of a thermostable DNA polymerase (Ambersham) and 20 pmol ofa template specific oligonucleotide PROBE primer5′-CTGGCGCCCACGTGGTCAA-3′ (SEQ ID NO: 48) (Operon). Primer extensionoccurs with three cycles of oligonucleotide primer hybridization andextension. The extension products were analyzed after denaturation fromthe template with 50 mM NH₄Cl and transfer of 150 nL each sample to asilicon chip preloaded with 150 nL of H3PA matrix material. The samplematerial was allowed to crystallize and was analyzed by MALDI-TOF(Bruker, PerSeptive). The SNP that is present in AKAP10-1 is a T to Ctransversion at nucleotide number 156277 of the sequence of a genomicclone of the AKAP10 gene (GenBank Accession No. AC005730) (SEQ ID NO:36). SEQ ID NO: 35: represents the nucleotide sequence of humanchromosome 17, which contains the genomic nucleotide sequence of thehuman AKAP10 gene, and SEQ ID NO: 36 represents the nucleotide sequenceof human chromosome 17, which contains the genomic nucleotide sequenceof the human AKAP10-1 allele. The mass of the primer used in the BioMassprobe reaction was 5500.6 daltons. In the presence of the SNP, theprimer is extended by the addition of ddC, which has a mass of 5773.8.The wildtype gene results in the addition of dT and ddG to the primer toproduce an extension product having a mass of 6101 daltons.

[0344] The frequency of the SNP was measured in a population of ageselected healthy individuals. Five hundred fifty-two (552) individualsbetween the ages of 18-39 years (276 females, 276 males) and 552individuals between the ages of 60-79 (184 females between the ages of60-69, 368 males between the age of 60-79) were tested for the presenceof the polymorphism localized in the non-translated 3′ region of AKAP10. Differences in the frequency of this polymorphism with increasingage groups were observed among healthy individuals. Statistical analysisshowed that the significance level for differences in the allelicfrequency for alleles between the “younger” and the “older” populationswas p=0.0009 and for genotypes was p=0.003. Differences between agegroups are significant. For the total population allele significance isp=0.0009, and genotype significance is p=0.003.

[0345] This marker led to the best significant result with regard toallele and genotype frequencies in the age-stratified population. FIG.19 shows the allele and genotype frequency in both genders as well as inthe entire population. For the latter, the significance for alleles wasp=0.0009 and for genotypes was p=0.003. The young and old populationswere in Hardy-Weinberg equilibrium. A preferential change of oneparticular genotype was not observed.

[0346] The polymorphism is localized in the non-translated 3′-region ofthe gene encoding the human protein kinase A anchoring protein (AKAP10).The gene is located on chromosome 17. Its structure includes 15 exonsand 14 intervening sequences (introns). The encoded protein isresponsible for the sub-cellular localization of the cAMP-dependentprotein kinase and, therefore, plays a key role in the G-proteinmediated receptor-signaling pathway (Huang et al. PNAS (1007)94:11184-11189). Since its localization is outside the coding region,this polymorphism is most likely in linkage disequilibrium (LD) withother non-synonymous polymorphisms that could cause amino acidsubstitutions and subsequently alter the function of the protein.Sequence comparison of different Genbank database entries concerningthis gene revealed further six potential polymorphisms of which two aresupposed to change the respective amino acid (see Table 3). TABLE 3 ExonCodon Nucleotides Amino acid 3 100 GCT > GCC Ala > Ala 4 177 AGT > GTGMet > Val 8 424 GGG > GGC Gly > Gly 10 524 CCG > CTG Pro > Leu 12 591GTG > GTC Val > Val 12 599 CGC > CGA Arg > Arg

[0347] Morbitity Marker 2: Human Protein Kinase A Anchoring Protein(AKAP10-5)

[0348] Discovery of AKAP10-5 Allele (SEQ ID NO: 33)

[0349] Genomic DNA was isolated from blood (as described above) ofseventeen (17) individuals with a genotype CC at the AKAP10-1 gene locusand a single heterozygous individual (CT) (as described). A targetsequence in the AKAP10-1 gene which encodes the C-terminal PKA bindingdomain was amplified using the polymerase chain reaction. PCR primerswere synthesized by OPERON using phosphoramidite chemistry.Amplification of the AKAP10-1 target sequence was carried out inindividual 50 μl PCR reaction with 25 ng of human genomic DNA templates.Each reaction containing I×PCR buffer (Qiagen, Valencia, Calif.), 200 μMdNTPs, IU Hotstar Taq polymerase (Qiagen, Valencia, Calif.), 4 mM MgCl₂,25 pmol of the forward primer (Ex13F) containing the universal primersequence and the target specific sequence 5′-TCC CAA AGT GCT GGA ATTAC-3′ (SEQ ID NO: 53), and 2 pmol of the reverse primer (Ex14R) 5′-GTCCAA TAT ATG CAA ACA GTT G-3′ (SEQ ID NO: 54). Thermal cycling wasperformed in 0.2 mL tubes or 96 well plate using an MJ Research ThermalCycler (MJ Research, Waltham, Mass.) (calculated temperature) with thefollowing cycling parameters: 94° C. for 5 min; 45 cycles; 94° C. for 20sec, 56° C. for 30 sec, 72° C. for 60 sec; 72° C. 3 min. Afteramplification the amplicons were purified using a chromatography (Mo BioLaboratories (Solana Beach, Calif.)).

[0350] The sequence of the 18 amplicons, representing the target region,was determined using a standard Sanger cycle sequencing method with 25nmol of the PCR amplicon, 3.2 uM DNA sequencing primer 5′-CCC ACA GCAGTT AAT CCT TC-3′(SEQ ID NO: 55), and chain terminating dRhodaminelabeled 2′, 3′ dideoxynucleotides (PE Biosystems, Foster City, Calif.)using the following cycling parameters: 96° C. for 15 seconds; 25cycles: 55° C. for 15 seconds, 60° C. for 4 minutes. The sequencingproducts precipitated by 0.3M NaOAc and ethanol. The precipitate wascentrifuged and dried. The pellets were resuspended in deionizedformamide and separated on a 5% polyacrylimide gel. The sequence wasdetermined using the “Sequencher” software (Gene Codes, Ann Arbor,Mich.).

[0351] The sequence of all 17 of the amplicons, which are homozygous forthe AKAP10-1 SNP of the amplicons, revealed a polymorphism at nucleotideposition 152171 (numbering for GenBank Accession No. AC005730 for AKAP10genomic clone (SEQ ID NO: 35)) with A replaced by G. This SNP also canbe designated as located at nucleotide 2073 of a cDNA clone of thewildtype AKAP10 (GenBank Accession No. AF037439) (SEQ ID NO: 31). Theamino acid sequence of the human AKAP10 protein is provided as SEQ IDNO: 34. This single nucleotide polymorphism was designated as AKAP10-5(SEQ ID NO: 33) and resulted in a substitution of a valine for anisoleucine residue at amino acid position 646 of the amino acid sequenceof human AKAP10 (SEQ ID NO: 32).

[0352] PCR Amplification and BiomassPROBE Assay Detection of AKAP10-5 ina Healthy Donor Population

[0353] The healthy population stratified by age is a very efficient anda universal screening tool for morbidity associated genes by allowingfor the detection of changes of allelic frequencies in the youngcompared to the old population. Individual samples of this healthypopulation base can be pooled to further increase the throughput.

[0354] Healthy samples were obtained through the blood bank of SanBernardino, Calif. Both parents of the blood donors were of Caucasianorigin. Practically a healthy subject, when human, is defined as humandonor who passes blood bank criteria to donate blood for eventual use inthe general population. These criteria are as follows: free ofdetectable viral, bacterial, mycoplasma, and parasitic infections; notanemic; and then further selected based upon a questionnaire regardinghistory (see FIG. 3). Thus, a healthy population represents an unbiasedpopulation of sufficient health to donate blood according to blood bankcriteria, and not further selected for any disease state. Typically suchindividuals are not taking any medications.

[0355] PCR primers were synthesized by OPERON using phosphoramiditechemistry. Amplification of the AKAP10 target sequence was carried outin a single 50 μl PCR reaction with 100 ng-1 μg of pooled human genomicDNAs in a 50 μl PCR reaction. Individual DNA concentrations within thepooled samples were present in equal concentration with the finalconcentration ranging from 1-25 ng. Each reaction contained 1×PCR buffer(Qiagen, Valencia, Calif.), 200 μM dNTPs, 1U Hotstar Taq polymerase(Qiagen, Valencia, Calif.), 4 mM MgCl₂, and 25 pmol of the forwardprimer containing the universal primer sequence and the target specificsequence 5′-AGCGGATAACAATTTCACACAGGGAGCTAGCTTGGAAGAT TGC-3′ (SEQ ID NO:41), 2 pmol of the reverse primer 5′-GTCCAATATATGCAAACAGTTG-3′ (SEQ IDNO: 54), and 10 pmol of a biotinylated universal primer complementary tothe 5′ end of the PCR amplicon BIO:5′-AGCGGATAACAATTTCACACAGG-3′ (SEQ IDNO: 43). After an initial round of amplification with the target withthe specific forward and reverse primer, the 5′ biotinylated universalprimer can then be hybridized and acted as a forward primer therebyintroducing a 5′ biotin capture moiety into the molecule. Theamplification protocol resulted in a 5′-biotinylated double stranded DNAamplicon and dramatically reduced the cost of high throughput genotypingby eliminating the need to 5′ biotin label every forward primer used ina genotyping.

[0356] Themal cycling was performed in 0.2 mL tubes or 96 well plateusing an MJ Research Thermal Cycler (calculated temperature) with thefollowing cycling parameters: 94° C. for 5 min; 45 cycles: 94° C. for 20sec, 56° C. for 30 sec; 72° C. for 60 sec; 72° C. 3 min.

[0357] Immobilization of DNA

[0358] The 50 μl PCR reaction was added to 25 μL of streptavidin coatedmagnetic beads (Dynal, Oslo, Norway), which were prewashed three timesand resuspended in 1M NH₄Cl, 0.06M NH₄OH. The 5′ end of one strand ofthe double stranded PCR amplicons were allowed to bind to the beads for15 minutes at room temperature. The beads were then collected with amagnet, and the supernatant containing unbound DNA was removed. Thehybridized but unbound strand was released from the double strandedamplicons by incubation in 100 mM NaOH and washing of the beads threetimes with 10 mM Tris pH 8.0.

[0359] Detection of AKAP10-5 using BiomassPROBE™ Assay

[0360] BiomassPROBE™ assay of primer extension analysis (see, U.S. Pat.No. 6,043,031) of donor population for AKAP 10-5 (SEQ ID NO: 33) wasperformed. Genotyping using these methods was carried out byresuspending the DNA coated magnetic beads in 26 mM Tris-HCL pH 9.5, 6.5mM MgCl₂, 50 mM dTTP, 50 mM each of ddCTP, ddATP, ddGTP, 2.5U of athermostable DNA polymerase (Ambersham), and 20 pmol of a templatespecific oligonucleotide PROBE primer 5′-ACTGAGCCTGCTGCATAA-3′ (SEQ IDNO: 44) (Operon). Primer extension occurs with three cycles ofoligonucleotide primer with hybridization and extension. The extensionproducts were analyzed after denaturation from the template with 50 mMNH₄Cl and transfer of 150 nL of each sample to a silicon chip preloadedwith 150 nl of H3PA matrix material. The sample material was allowed tocrystallize and analyzed by MALDI-TOF (Bruker, PerSeptive). The primerhas a mass of 5483.6 daltons. The SNP results in the addition of a ddCto the primer, giving a mass of 5756.8 daltons for the extended product.The wild type results in the addition a T and ddG to the primer giving amass of 6101 daltons.

[0361] The frequency of the SNP was measured in a population of ageselected healthy individuals. Seven hundred thirteen (713) individualsunder 40 years of age (360 females, 353 males) and 703 individuals over60 years of age (322 females, 381 males) were tested for the presence ofthe SNP, AKAP10-5 (SEQ ID NO: 33). Results are presented below in Table4. TABLE 4 AKAP10-5 (2073V) frequency comparison in 2 age groups <40 >60delta G allele Female Alleles *G 38.6 34.6 4.0 *A 61.4 65.4 Genotypes G13.9 11.8 2.1 GA 49.4 45.7 A 36.7 42.5 Male Alleles *G 41.4 37.0 4.4 *A58.6 63.0 Genotypes G 18.4 10.8 7.7 GA 45.9 52.5 A 35.7 36.7 TotalAlleles *G 40.0 35.9 4.1 *A 60.0 64.1 Genotypes G 16.1 11.2 4.9 GA 47.749.4 A 36.2 39.4

[0362]FIG. 20 graphically shows these results of allele and genotypedistribution in the age and sex stratified Caucasian population.

[0363] Morbidity Marker 3: Human Methionine Sulfoxide Reductase A (msrA)

[0364] The age-related allele and genotype frequency of this marker inboth genders and the entire population is shown in FIG. 21. The decreaseof the homozygous CC genotype in the older male population is highlysignificant.

[0365] Methionine Sulfoxide Reductase A (#63306)

[0366] PCR Amplification and BiomassPROBE assay detection of the humanmethioine sulfoxide reductase A (h-msr-A) in a healthy donor population

[0367] PCR Amplification of Donor Population for h-msr-A

[0368] PCR primers were synthesized by OPERON using phosphoramiditechemistry. Amplification of the AKAP10 target sequence was carried outin single 50 μl PCR reaction with 100 ng-1 ug of pooled human genomicDNA templates in a 50 μl PCR reaction. Individual DNA concentrationswithin the pooled samples were present in an equal concentration withthe final concentration ranging from 1-25 ng. Each reaction containing IX PCR buffer (Qiagen, Valencia, Calif.), 200 μM dNTPs, 1U Hotstar Taqpolymerase (Qiagen, Valencia, Calif.), 4 mM MgCl₂, 25 pmol of theforward primer containing the universal primer sequence and the targetspecific sequence 5′-TTTCTCTGCACAGAGAGGC-3′ (SEQ ID NO: 49), 2 pmol ofthe reverse primer 5′-AGCGGATAACAATTTCACACAGGGCTGAAATCCTTCGCTTTACC-3′(SEQ ID NO: 50), and 10 pmol of a biotinylated universal primercomplementary to the 5′ end of the PCR amplicon5′-AGCGGATAACAATTTCACACAGG-3′ (SEQ ID NO: 51). After an initial round ofamplification of the target with the specific forward and reverseprimers, the 5′ biotinylated universal primer was then hybridized andacted as a reverse primer thereby introducing a 3′ biotin capture moietyinto the molecule. The amplification protocol results in a5′-biotinylated double stranded DNA amplicon and dramatically reducesthe cost of high throughput genotyping by eliminating the need to 5′biotin label each forward primer used in a genotyping. Thermal cyclingwas performed in 0.2 mL tubes or 96 well plate using an MJ ResearchThermal Cycler (calculated temperature) with the following cyclingparameters: 94° C. for 5 min; 45 cycles: 94° C. for 20 sec, 56° C. for30 sec, 72° C. for 60 sec; 72° C. 3 min.

[0369] Immobilization of DNA

[0370] The 50 μl PCR reaction was added to 25 ul of streptavidin coatedmagnetic bead (Dynal) prewashed three times and resuspended in 1M NH₄Cl,0.06M NH₄OH. The PCR amplicons were allowed to bind to the beads for 15minutes at room temperature. The beads were then collected with a magnetand the supernatant containing unbound DNA was removed. The unboundstrand was released from the double stranded amplicons by incubation in100 mM NaOH and washing of the beads three times with 10 mM Tris pH 8.0.

[0371] BiomassPROBE Assay Analysis of Donor Population for h-msr A

[0372] Genotyping using the BiomassPROBE assay methods was carried outby resuspending the DNA coated magnetic beads in 26 mM Tris-HCl pH 9.5,6.5 mM MgCl₂, 50 mM of dTTPs and 50 mM each of ddCTP, ddATP, ddGTP, 2.5Uof a thermostable DNA polymerase (Ambersham), and 20 pmol of a templatespecific oligonucleotide PROBE primer 5′-CTGAAAAGGGAGAGAAAG-3′ (Operon)(SEQ ID NO: 52). Primer extension occurs with three cycles ofoligonucleotide primer with hybridization and extension. The extensionproducts were analyzed after denaturation from the template with 50 mMNH₄Cl and transfer of 150 nl each sample to a silicon chip preloadedwith 150 nl of H3PA matrix material. The sample material was allowed tocrystallize and analyzed by MALDI-TOF (Bruker, PerSeptive). The SNP isrepresented as a T to C tranversion in the sequence of two ESTs. Thewild type is represented by having a T at position 128 of GenBankAccession No. AW 195104, which represents the nucleotide sequence of anEST which is a portion of the wild type human msrA gene (SEQ ID NO: 39).The SNP is presented as a C at position 129 of GenBank Accession No. AW874187, which represents the nucleotide sequence of an EST which is aportion of an allele of the human msrA gene (SEQ ID NO: 40).

[0373] In a genomic sequence the SNP is represented as an A to Gtransversion. The primer utilized in the BioMass probe reaction had amass of 5654.8 daltons. In the presence of the SNP the primer isextended by the incorporation of a ddC and has a mass of 5928. In thepresence of the wildtype the primer is extended by adding a dT and a DDCto produce a mass of 6232.1 daltons.

[0374] The frequency of the SNP was measured in a population of ageselected healthy individuals. Five hundred fifty-two (552) individualsbetween the ages of 18-39 years (276 females, 276 males and 552individuals between the age of 60-79 (184 females between the ages of60-69, 368 males between the age of 60-79) were tested for the presenceof the polymorphism localized in the nontranslated 3′ region of h-msr-A.

[0375] Genotype difference between male age group among healthyindividuals is significant. For the male population allele significanceis p=0.0009 and genotype significance is p=0.003. The age-related alleleand genotype frequency of this marker in both genders and the entirepopulation is shown in FIG. 21. The decrease of the homozygous CCgenotype in the older male population is highly significant.

[0376] The polymorphism is localized in the non-translated 3′-region ofthe gene encoding the human methionine sulfoxide reductase (h-msrA). Theexact localization is 451 base pairs downstream the stop codon (TAA). Itis likely that this SNP is in linkage disequilibrium (LD) with anotherpolymorphism more upstream in the coding or promoter region; thus, itdoes not directly cause morbidity. The enzyme methionine sulfoxidereductase has been proposed to exhibit multiple biological functions. Itcan serve to repair oxidative protein damage but also play an importantrole in the regulation of proteins by activation or inactivation oftheir biological functions (Moskovitz et al. (1990) PNAS95:14071-14075). It has also been shown that its activity issignificantly reduced in brain tissues of Alzheimer patients (Gabbita etal., (1999) J. Neurochem 73:1660-1666). It is scientifically conceivablethat proteins involved in the metabolism of reactive oxygen species areassociated to disease.

[0377] Conclusion

[0378] The use of the healthy population provides for the identificationof morbidity markers. The identification of proteins involved in theG-protein coupled signaling transduction pathway or in thedetoxification of oxidative stress can be considered as convincingresults. Further confirmation and validation of other potentialpolymorphisms already identified in silico in the gene encoding thehuman protein kinase A anchoring protein could even provide strongerassociation to morbidity and demonstrate that this gene product is asuitable pharmaceutical or diagnostic target.

EXAMPLE 4

[0379] MALDI-TOF Mass Spectrometry Analysis

[0380] All of the products of the enzyme assays listed below wereanalyzed by MALDI-TOF mass spectrometry. A diluted matrix solution (0.15μL) containing of 10:1 3-hydroxypicolinic acid:ammonium citrate in 1:1water:acetonitrile diluted 2.5-fold with water was pipetted onto aSpectroChip (Sequenom, Inc.) and was allowed to crystallize. Then, 0.15μL of sample was added. A linear PerSeptive Voyager DE mass spectrometeror Bruker Biflex MALDI-TOF mass spectrometer, operating in positive ionmode, was used for the measurements. The sample plates were kept at 18.2kV for 400 nm after each UV laser shot (approximate 250 laser shotstotal), and then the target voltage was raised to 20 kV. The originalspectra were digitized at 500 MHz.

EXAMPLE 5

[0381] Sample Conditioning

[0382] Where indicated in the examples below, the products of theenzymatic digestions were purified with ZipTips (Millipore, Bedford,Mass.). The ZipTips were pre-wetted with 10 μL 50% acetonitrile andequilibrated 4 times with 10 μl 0.1 M TEAAc. The oligonucleotidefragments were bound to the C18 in the ZipTip material by continuousaspiration and dispension of each sample into the ZipTip. Each digestedoligonucleotide was conditioned by washing with 10 μL 0.1 M TEAAc,followed by 4 washing steps with 10 μL H₂O. DNA fragments were elutedfrom the Ziptip with 7 μL 50% acetonitrile.

[0383] Any method for condition the samples can be employed. Methods forconditioning, which generally is used to increase peak resolution, arewell known (see, e.g., International PCT application No. WO 98/20019).

EXAMPLE 6

[0384] DNA Glycosylase-Mediated Sequence Analysis

[0385] DNA Glycosylases modifies DNA at each position that a specificnucleobase resides in the DNA, thereby producing abasic sites. In asubsequent reaction with another enzyme, a chemical, or heat, thephosphate backbone at each abasic site can be cleaved.

[0386] The glycosylase utilized in the following procedures wasuracil-DNA glycosylase (UDG). Uracil bases were incorporated into DNAfragments in each position that a thymine base would normally occupy byamplifying a DNA target sequence in the presence of uracil. Each uracilsubstituted DNA amplicon was incubated with UDG, which cleaved eachuracil base in the amplicon, and was then subjected to conditions thateffected backbone cleavage at each abasic site, which produced DNAfragments. DNA fragments were subjected to MALDI-TOF mass spectrometryanalysis. Genetic variability in the target DNA was then assessed byanalyzing mass spectra.

[0387] Glycosylases specific for nucleotide analogs or modifiednucleotides, as described herein, can be substituted for UDG in thefollowing procedures. The glycosylase methods described hereafter, inconjunction with phosphate backbone cleavage and MALDI, can be used toanalyze DNA fragments for the purposes of SNP scanning, bacteria typing,methylation analysis, microsatellite analysis, genotyping, andnucleotide sequencing and re-sequencing.

[0388] A. Genotyping

[0389] A glycosylase procedure was used to genotype the DNA sequenceencoding UCP-2 (Uncoupling Protein 2). The sequence for UCP-2 isdeposited in GenBank under accession number AF096289. The sequencevariation genotyped in the following procedure was a cytosine (C-allele)to thymine (T-allele) variation at nucleotide position 4790, whichresults in a alanine to valine mutation at position 55 in the UCP-2polypeptide.

[0390] DNA was amplified using a PCR procedure with a 50 μL reactionvolume containing of 5 pmol biotinylated primer having the sequence5′-TGCTTATCCCTGTAGCTACCCTGTCTTGGCCTTGCAGATCCAA-3′ (SEQ ID NO: 91), 15pmol non-biotinylated primer having the sequence5′-AGCGGATAACAATTTCACACAGGCCATCACACCGCGGTACTG-3′ (SEQ ID NO: 92), 200 μMdATP, 200 μM dCTP, 200 μM dGTP, 600 μM dUTP (to fully replace dTTP), 1.5mM to 3 mM MgCl₂, 1 U of HotStarTaq polymerase, and 25 ng of CEPH DNA.Amplification was effected with 45 cycles at an annealing temperature of56° C.

[0391] The amplification product was then immobilized onto a solidsupport by incubating 50 μL of the amplification reaction with 5 μL ofprewashed Dynabeads for 20 minutes at room temperature. The supernatantwas removed, and the beads were incubated with 50 μL of 0.1 M NaOH for 5minutes at room temperature to denature the double-stranded PCR productin such a fashion that single-stranded DNA was linked to the beads. Thebeads were then neutralized by three washes with 50 μL 10 mM TrisHCl (pH8). The beads were resuspended in 10 μL of a 60 mM TrisHCl/1 mM EDTA (pH7.9) solution, and 1 U uracil DNA glycosylase was added to the solutionfor 45 minutes at 37° C. to remove uracil nucleotides present in thesingle-stranded DNA linked to the beads. The beads were then washed twotimes with 25 μL of 10 mM TrisHCl (pH 8) and once with 10 μL of water.The biotinylated strands were then eluted from the beads with 12 μL of 2M NH₄OH at 60° C. for 10 minutes. The backbone of the DNA was cleaved byincubating the samples for 10 min at 95° C. (with a closed lid), andammonia was evaporated from the samples by incubating the samples for 11min at 80° C.

[0392] The cleavage fragments were then analyzed by MALDI-TOF massspectrometry as described in Example 4. The T-allele generated a uniquefragment of 3254 Daltons. The C-allele generated a unique fragment of4788 Daltons. These fragements were distinguishable in mass spectra.Thus, the above-identified procedure was successfully utilized togenotype individuals heterozygous for the C-allele and T-aliele inUCP-2.

[0393] B. Glycosylase Analysis Utilizing Pooled DNA Samples

[0394] The glycosylase assay was conducted using pooled samples todetect genetic variability at the UCP-2 locus. DNA of known genotype waspooled from eleven individuals and was diluted to a fixed concentrationof 5 ng/μL. The procedure provided in Example 3A was followed using 2pmol of forward primer having a sequence of5′-CCCAGTCACGACGTTGTAAAACGTCTTGGCCTTGCAGATCCAAG-3′ (SEQ ID NO: 93) and15 pmol of reverse primer having the sequence5′-AGCGGATAACAATTTCACACAGGCCATCACACCGCGGTACTG-3′ (SEQ ID NO: 94). Inaddition, 5 pmol of biotinylated primer having the sequence5′bioCCCAGTCACGACGTTGTAAAACG 3′ (SEQ ID NO: 97) can be introduced to thePCR reaction after about two cycles. The fragments were analyzed viaMALDI-TOF mass spectroscopy (Example 4). As determined in Example 3A,the T-allele, which generated a unique fragment of 3254 Daltons, couldbe distinguished in mass spectra from the C-allele, which generated aunique fragment of 4788 Daltons. Allelic frequency in the pooled sampleswas quantified by integrating the area under each signal correspondingto an allelic fragment. Integration was accomplished by handcalculations using equations well known to those skilled in the art. Inthe pool of eleven samples, this procedure suggested that 40.9% of theindividuals harbored the T allele and 59.09% of the individuals harboredthe C allele.

[0395] C. Glycosylase-Mediated Microsatellite Analysis

[0396] A glycosylase procedure was utilized to identify microsatellitesof the Bradykinin Receptor 2 (BKR-2) sequence. The sequence for BKR-2 isdeposited in GenBank under accession number X86173. BKR-2 includes a SNPin the promoter region, which is a C to T variation, as well as a SNP ina repeated unit, which is a G to T variation. The procedure provided inExample 3A was utilized to identify the SNP in the promotor region, theSNP in the microsattelite repeat region, and the number of repeatedunits in the microsattelite region of BKR-2. Specifically, a forward PCRprimer having the sequence 5′-CTCCAGCTGGGCAGGAGTGC-3′ (SEQ ID NO: 95)and a reverse primer having the sequence 5′-CACTTCAGTCGCTCCCT-3′ (SEQ IDNO: 96) were utilized to amplify BKR-2 DNA in the presence of uracil.The amplicon was fragmented by UDG followed by backbone cleavage. Thecleavage fragments were analyzed by MALDI-TOF mass spectrometry asdescribed in Example 4.

[0397] With regard to the SNP in the BKR-2 promotor region having a C toT variation, the C-allele generated a unique fragment having a mass of7342.4 Daltons, and the T-allele generated a unique fragment having amass of 7053.2 Daltons. These fragments were distinguishable in massspectra. Thus, the above-identified procedure was successfully utilizedto genotype individuals heterozygous for the C-allele and T-allele inthe promotor region of BKR-2.

[0398] With regard to the SNP in the BKR-2 repeat region having a G to Tvariation, the T-allele generated a unique fragment having a mass of1784 Daltons, which was readily detected in a mass spectrum. Hence, thepresence of the T-allele was indicative of the G to T sequence variationin the repeat region of BKR-2.

[0399] In addition, the number of repeat regions was distinguishedbetween individuals having two repeat sequences and individuals havingthree repeat sequences in BKR-2. The DNA of these individuals did notharbor the G to T sequence variation in the repeat sequence as eachrepeat sequence contained a G at the SNP locus. The number of repeatregions was determined in individual samples by calculating the areaunder a signal corresponding to a unique DNA fragment having a mass of2771.6 Daltons. This signal in spectra generated from individuals havingtwo repeat regions had an area that was thirty-three percent less thanthe area under the same signal in spectra generated from individualshaving three repeat regions. Thus, the procedures discussed above can beutilized to genotype individuals for the number of repeat sequencespresent in BKR-2.

[0400] D. Bisulfite Treatment Coupled with Glycosylase Digestion

[0401] Bisulfite treatment of genomic DNA can be utilized to analyzepositions of methylated cytosine residues within the DNA. Treatingnucleic acids with bisulfite deaminates cytosine residues to uracilresidues, while methylated cytosine remains unmodified. Thus, bycomparing the sequence of a PCR product generated from genomic DNA thatis not treated with bisulfite with the sequence of a PCR productgenerated from genomic DNA that is treated with bisulfite, the degree ofmethylation in a nucleic acid as well as the positions where cytosine ismethylated can be deduced.

[0402] Genomic DNA (2 μg) was digested by incubation with 1 μL of arestriction enzyme at 37° C. for 2 hours. An aliquot of 3 M NaOH wasadded to yield a final concentration of 0.3M NaOH in the digestionsolution. The reaction was incubated at 37° C. for 15 minutes followedby treatment with 5.35M urea, 4.44M bisulfite, and 10 mM hydroquinone,where the final concentration of hydroquinone is 0.5 mM.

[0403] The sample that was treated with bisulfite (sample A) wascompared to the same digestion sample that had not undergone bisulfitetreatment (sample B). After sample A was treated with bisulfite asdescribed above, sample A and sample B were amplified by a standard PCRprocedure. The PCR procedure included the step of overlaying each samplewith mineral oil and then subjecting the sample to thermocycling (20cycles of 15 minutes at 55° C. followed by 30 seconds at 95° C.). ThePCR reaction contained four nucleotide bases, C, A, G, and U. Themineral oil was removed from each sample, and the PCR products werepurified with glassmilk. Sodium iodide (3 volumes) and glassmilk (5 μL)were added to samples A and B. The samples were then placed on ice for 8minutes, washed with 420 μL cold buffer, centrifuged for 10 seconds, andthe supernatant fractions were removed. This process was repeated twiceand then 25 μL of water was added. Samples were incubated for 5 minutesat 37° C., were centrifuged for 20 seconds, and the supernatant fractionwas collected, and then this incubation/centrifugation/supernatantfraction collection procedure was repeated. 50 μL 0.1 M NaOH was thenadded to the samples to denature the DNA. The samples were incubated atroom temperature for 5 minutes, washed three times with 50 μL of 10 mMTrisHCl (pH 8), and resuspended in 10 μL 60 mM TrisHCl/1 mM EDTA, pH7.9.

[0404] The sequence of PCR products from sample A and sample B were thentreated with 2U of UDG (MBI Fermentas) and then subjected to backbonecleavage, as described herein. The resulting fragments from each ofsample A and sample B were analyzed by MALDI-TOF mass spectroscopy asdescribed in Example 4. Sample A gave rise to a greater number offragments than the number of fragments arising from sample B, indicativethat the nucleic acid harbored at least one methylated cytosine moiety.

EXAMPLE 7

[0405] Fen-Ligase-Mediated Haplotyping

[0406] Haplotyping procedures permit the selection of a fragment fromone of an individual's two homologous chromosomes and to genotype linkedSNPs on that fragment. The direct resolution of haplotypes can yieldincreased information content, improving the diagnosis of any linkeddisease genes or identifying linkages associated with those diseases. Inprevious studies, haplotypes were typically reconstructed indirectlythrough pedigree analysis (in cases where pedigrees were available)through laborious and unreliable allele-specific PCR or throughsingle-molecule dilution methods well known in the art.

[0407] A haplotyping procedure was used to determine the presence of twoSNPs, referred to as SNP1 and SNP2, located on one strand in a DNAsample. The haplotyping procedure used in this assay utilized Fen-1, asite-specific “flap” endonuclease that cleaves DNA “flaps” created bythe overlap of two oligonucleotides hybridized to a target DNA strand.The two overlapping oligonucleotides in this example were short arm andlong arm allele-specific adaptors. The target DNA was an amplifiednucleic acid that had been denatured and contained SNP1 and SNP2.

[0408] The short arm adaptor included a unique sequence not found in thetarget DNA. The 3′ distal nucleotide of the short arm adaptor wasidentical to one of the SNP1 alleles. Moreover, the long arm adaptorincluded two regions: a 3′ region complementary to the short arm and a5′ gene-specific region complementary to the fragment of interestadjacent to the SNP. If there was a match between the adaptor and one ofthe homologues, the Fen enzyme recognized and cleaved the overlappingflap. The short arm of the adaptor was then ligated to the remainder ofthe target fragment (minus the SNP site). This ligated fragment was usedas the forward primer for a second PCR reaction in which only theligated homologue was amplified. The second PCR product (PCR2) was thenanalyzed by mass spectrometry. If there was no match between theadaptors and the target DNA, there was no overlap, no cleavage by Fen-1,and thus no PCR2 product of interest.

[0409] If there was more than one SNP in the sequence of interest, thesecond SNP (SNP2) was found by using an adaptor that was specific forSNP2 and hybridizing the adaptor to the PCR2 product containing thefirst SNP. The Fen-ligase and amplification procedures were repeated forthe PCR2 product containing the first SNP. If the amplified productyielded a second SNP, then SNP1 and SNP2 were on the same fragment.

[0410] If the SNP is unknown, then four allele-specific adaptors (e.g.C, G, A, and T) can be used to hybridize with the target DNA. Thesubstrates are then treated with the Fen-ligase protocol, includingamplification. The PCR2 products can be analyzed by PROBE, as describedherein, to determine which adaptors were hybridized to the DNA targetand thus identify the SNPs in the sequence.

[0411] A Fen-ligase assay was used to detect two SNPs present in FactorVII. These SNPs are located 814 base pairs apart from each other. SNP1was located at position 8401 (C to T), and SNP2 was located at 9215 (Gto A).

[0412] A. First Amplification Step

[0413] A PCR product (PCR1) was generated for a known heterozygousindividual at SNP1, a short distance from the 5′ end of the SNP.Specifically, a 10 μL PCR reaction was performed by mixing 1.5 mM MgCl₂,200 μM of each dNTP, 0.5 U HotStar polymerase, 0.1 μM of a forwardprimer having the sequence 5′-GCG CTC CTG TCG GTG CCA (SEQ ID NO: 56),0.1 μM of a reverse primer having the sequence 5′-GCC TGA CTG GTG GGGCCC (SEQ ID NO: 57), and 1 ng of genomic DNA. The annealing temperaturewas 58° C., and the amplification process yielded fragments that were861 bp in length.

[0414] The PCR1 reaction mixture was divided in half and was treatedwith an exonuclease 1/SAP mixture (0.22 μL mixture/5 μL PCR1 reaction)which contained 1.0 μL SAP and 0.1 μL exon1. The exonuclease treatmentwas done for 30 minutes at 37° C. and then 20 minutes at 85° C. todenature the DNA.

[0415] B. Adaptor Oligonucleotides

[0416] A solution of allele-specific adaptors (C and T), containing ofone long and one short oligonucleotide per adaptor, was prepared. Thelong arm and short arm oligonucleotides of each adaptor (10 μM) weremixed in a 1:1 ratio and heated for 30 seconds at 95° C. The temperaturewas reduced in 2° C. increments to 37° C. for annealing. The C-adaptorhad a short arm sequence of 5′-CAT GCA TGC ACG GTC (SEQ ID NO: 58) and along arm sequence of 5′-CAG AGA GTA CCC CTC GAC CGT GCA TGC ATG (SEQ IDNO: 59). Hence, the long arm of the adaptor was 30 bp (15 bpgene-specific), and the short arm was 15 bp. The T-adaptor had a shortarm sequence of 5′-CAT GCA TGC ACG GTT (SEQ ID NO: 60) and a long armsequence of 5′-GTA CGT ACG TGC CAA CTC CCC ATG AGA GAC (SEQ ID NO: 61).The adaptor could also have a hairpin structure in which the short andlong arm are separated by a loop containing of 3 to 10 nucleotides (SEQID NO: 118).

[0417] C. FEN-ligase Reaction

[0418] In two tubes (one tube for each allele-specific adaptor persample) was placed a solution (Solution A) containing of 3.5 μl 10 mM16% PEG/50 mM MOPS, 1.2 μl 25 mM MgCl₂, 1.5 μl 10X Ampligase Buffer, and2.5 μl PCR1. Each tube containing Solution A was incubated at 95° C. for5 minutes to denature the PCR1 product. A second solution (Solution B)containing of 1.65 μl Ampligase (Thermostable ligase, EpicentreTechnologies), 1.65 μl 200 ng/μl MFEN (from Methanocuccus jannaschil),and 3.0 μl of an allel specific adaptor (C or T) was prepared. Thus,different variations of Solution B, each variation containing ofdifferent allele-specific adaptors, were made. Solution B was added toSolution A at 95° C. and incubated at 55° C. for 3 hours. The totalreaction volume was 15.0 μl per adaptor-specific reaction. For abi-allelic system, 2×15.0 μl reactions were required.

[0419] The Fen-ligase reaction in each tube was then deactivated byadding 8.0 μl 10 mM EDTA. Then, 1.0 μl exoIII/Buffer (70%/30%) solutionwas added to each sample and incubated 30 minutes at 37° C., 20 minutesat 70° C. (to deactivate exoIII), and 5 minutes at 95° C. (to denaturethe sample and dissociate unused adaptor from template). The sampleswere cooled in an ice slurry and purified on UltraClean PCR Clean-up(MoBio) spin columns which removed all fragments less than 100 basepairs in length. The fragments were eluted with 50 μl H₂O.

[0420] D. Second Amplification Step

[0421] A second amplification reaction (PCR2) was conducted in eachsample tube using the short arm adaptor (C or T) sequence as the forwardprimer (minus the SNP1 site). Only the ligated homologue was amplified.A standard PCR reaction was conducted with a total volume of 10.0 μlcontaining of 1×Buffer (final concentration), 1.5 mM final concentrationMgCl₂, 200 μM final concentration dNTPs, 0.5 U HotStar polymerase, 0.1μM final concentration forward primer 5′-CAT GCA TGC ACG GT (SEQ ID NO:62), 0.1 μM final concentration reverse primer 5′-GCC TGA CTG GTG GGGCCC (SEQ ID NO: 63), and 1.0 μl of the purified FEN-ligase reactionsolution. The annealing temperature was 58° C. The PCR2 product wasanalyzed by MALDI TOF mass spectroscopy as described in Example 4. Themass spectrum of Fen SNP1 showed a mass of 6084.08 Daltons, representingthe C allele.

[0422] E. Genotyping Additional SNPs

[0423] The second SNP (SNP2) can be found by using an adaptor that isspecific for SNP2 and hybridizing that adaptor to the PCR2 productcontaining the first SNP. The Fen-ligase and amplification proceduresare repeated for the PCR2 product containing the first SNP. If theamplified product yields a second SNP, then SN1 and SN2 are on the samefragment. The mass spectrum of SNP2, representing the T allele, showed amass of 6359.88 Daltons.

[0424] This assay also can be performed upon pooled DNA to yieldhaplotype frequencies as described herein. The Fen-ligase assay can beused to analyze multiplexes as described herein.

EXAMPLE 8

[0425] Nickase-Mediated Sequence Analysis

[0426] A DNA nickase, or DNase, was used to recognize and cleave onestrand of a DNA duplex. NY2A nickase and NYS1 nickase (Megabase), whichcleave DNA at the following sites:

[0427] NY2A: 5′ . . . R AG . . . 3′

[0428] 340 . . . Y⇓TC . . . 5′ where R=A or G and Y=C or T

[0429] NYS1: 5′ . . . ⇓CC[A/G/T] . . . 3′

[0430] 3′ . . . GG[T/C/A] . . . 5′

[0431] were used.

[0432] A. Nickase Digestion

[0433] Tris-HCl (10 mM), KCl (10 mM, pH 8.3), magnesium acetate (25 mM),BSA (1 mg/mL), and 6 U of Cvi NY2A or Cvi NYS1 Nickase (MegabaseResearch) were added to 25 pmol of double-stranded oligonucleotidetemplate having a sequence of 5′-CGC AGG GTT TCC TCG TCG CAC TGG GCA TGTG-3′ (SEQ ID NO: 90, Operon, Alameda, Calif.) synthesized using standardphosphoramidite chemistry. With a total volume of 20 μL, the reactionmixture was incubated at 37° C. for 5 hours, and the digestion productswere purified using ZipTips (Millipore, Bedford, Mass.) as described inExample 5. The samples were analyzed by MALDI-TOF mass spectroscopy asdescribed in Example 1. The nickase Cvi NY2A yielded three fragmentswith masses 4049.76 Daltons, 5473.14 Daltons, and 9540.71 Daltons. TheCvi NYS1 nickase yielded fragments with masses 2063.18 Daltons, 3056.48Daltons, 6492.81 Daltons, and 7450.14 Daltons.

[0434] B. Nickase Digestion of Pooled Samples

[0435] DQA (HLA ClassII-DQ Alpha, expected fragment size=225 bp) wasamplified from the genomic DNA of 100 healthy individuals. DQA wasamplified using standard PCR chemistry in a reaction having a totalvolume of 50 μL containing of 10 mM Tris-HCl, 10 mM KCl (pH 8.3), 2.5 mMMgCl₂, 200 μM of each dNTP, 10 pmol of a forward primer having thesequence 5′-GTG CTG CAG GTG TAA ACT TGT ACC AG-3′(SEQ ID NO: 64), 10pmol of a reverse primer having the sequence 5′-CAC GGA TCC GGT AGC AGCGGT AGA GTT G-3′(SEQ ID NO: 65), 1 U DNA polymerase (Stoffel fragment,Perkin Elmer), and 200 ng human genomic DNA (2 ng DNA/individual). Thetemplate was denatured at 94° C. for 5 minutes. Thermal cycling wascontinued with a touch-down program that included 45 cycles of 20seconds at 94° C., 30 seconds at 56° C., 1 minute at 72° C., and a finalextension of 3 minutes at 72° C. The crude PCR product was used in thesubsequent nickase reaction.

[0436] The unpurified PCR product was subjected to nickase digestion.Tris-HCl (10 mM), KCl (10 mM, pH 8.3), magnesium acetate (25 mM), BSA (1mg/mL), and 5 U of Cvi NY2A or Cvi NYS1 Nickase (Megabase Research) wereadded to 25 pmol of the amplified template with a total reaction volumeof 20 μL. The mixture was then incubated at 37° C. for 5 hours. Thedigestion products were purified with either ZipTips (Millipore,Bedford, Mass.) as described in Example 5. The samples were analyzed byMALDI-TOF mass spectroscopy as described in Example 4. This assay alsocan be used to do multiplexing and standardless genotyping as describedherein.

[0437] To simplify the nickase mass spectrum, the two complementarystrands can be separated after digestion by using a single-strandedundigested PCR product as a capture probe. This probe (preparation shownbelow in Example 8C) can be hybridized to the nickase fragments inhybridization buffer containing 200 mM sodium citrate and 1% blockingreagent (Boehringer Mannheim). The reaction is heated to 95° C. for 5minutes and cooled to room temperature over 30 minutes by using athermal cycler (PTC-200 DNA engine, MJ Research, Waltham, Mass.). Thecapture probe-nickase fragment is immobilized on 140 μg ofstreptavidin-coated magnetic beads. The beads are subsequently washedthree times with 70 mM ammonium citrate. The captured single-strandednickase fragments are eluted by heating to 80° C. for 5 minutes in 5 μLof 50 mM ammonium hydroxide.

[0438] C. Preparation of Capture Probe

[0439] The capture probe is prepared by amplifying the human β-globingene (3′ end of intron 1 to 5′ end of exon 2) via PCR methods in a totalvolume of 50 μL containing of GeneAmp 1XPCR Buffer II, 10 mM Tris-HCl,pH 8.3, 50 mM KCl, 2 mM MgCl₂, 0.2 mM dNTP mix, 10 pmol of each primer(forward primer 5′-ACTGGGCATGTGGAGACAG-3′(SEQ ID NO: 66) andbiotinylated reverse primer bio5′-GCACTTTCTTGCCATGAG-3′(SEQ ID: 67), 2 Uof AmpliTaq Gold, and 200 ng of human genomic DNA. The template isdenatured at 94° C. for 8 minutes. Thermal cycling is continued with atouch-down program that included 11 cycles of 20 seconds at 94° C., 30seconds at 64° C., 1 minute at 72° C.; and a final extension of 5minutes at 72° C. The amplicon is purified using UltraClean™ PCRclean-up kit (MO Bio Laboratories, Solano Beach, Calif.).

EXAMPLE 9

[0440] Multiplex Type IIS SNP Assay

[0441] A Type IIS assay was used to identify human gene sequences withknown SNPs. The Type IIS enzyme used in this assay was Fok I whicheffected double-stranded cleavage of the target DNA. The assay involvedthe steps of amplification and Fok I treatment of the amplicon. In theamplification step, the primers were designed so that each PCR productof a designated gene target was less than 100 bases such that a Fok Irecognition sequence was incorporated at the 5′ and 3′ end of theamplicon. Therefore, the fragments that were cleaved by Fok I included acenter fragment containing the SNP of interest.

[0442] Ten human gene targets with known SNPs were analyzed by thisassay. Sequences of the ten gene targets, as well as the primers used toamplify the target regions, are found in Table 5. The ten targets werelipoprotein lipase, prothrombin, factor V, cholesterol ester transferprotein (CETP), factor VII, factor XIII, HLA-H exon 2, HLA-H exon 4,methylenetetrahydrofolate reductase (MTHR), and P53 exon 4 codon 72.

[0443] Amplification of the ten human gene sequences were carried out ina single 50 μL volume PCR reaction with 20 ng of human genomic DNAtemplate in 5 PCR reaction tubes. Each reaction vial contained 1×PCRbuffer (Qiagen), 200 μM dNTPs, 1 U Hotstar Taq polymerase (Qiagen), 4 mMMgCl₂, and 10 pmol of each primer. US8, having sequence of5′TCAGTCACGACGTT3′(SEQ ID NO: 68), and US9, having sequence of5′CGGATAACAATTTC3′(SEQ ID NO: 69), were used for the forward and reverseprimers respectively. Moreover, the primers were designed such that aFok I recognition site was incorporated at the 5′ and 3′ ends of theamplicon. Thermal cycling was performed in 0.2 mL tubes or a 96 wellplate using a MJ Research Thermal Cycler (calculated temperature) withthe following cycling parameters: 94° C. for 5 minutes; 45 cycles: 94°C. for 20 seconds, 56° C. for 20 seconds, 72° C. for 60 seconds; and 72°C. for 3 minutes.

[0444] Following PCR, the sample was treated with 0.2 U Exonuclease I(Amersham Pharmacia) and S Alkaline Phosphotase (Amersham Pharmacia) toremove the unincorporated primers and dNTPs. Typically, 0.2 U ofexonuclease I and SAP were added to 5 μL of the PCR sample. The samplewas then incubated at 37° C. for 15 minutes. Exonuclease I and SAP werethen inactivated by heating the sample up to 85° C. for 15 minutes. FokI digestion was performed by adding 2 U of Fok I (New England Biolab) tothe 5 uL PCR sample and incubating at 37° C. for 30 minutes. Since theFok I restriction sites are located on both sides of the amplicon, the5′ and 3′ cutoff fragments have higher masses than the center fragmentcontaining the SNP. The sample was then purified by anion exchange andanalyzed by MALDI-TOF mass spectrometry as described in Example 4. Themasses of the gene fragments from this multiplexing experiment arelisted in Table 6. These gene fragments were resolved in mass spectrathereby allowing multiplex analysis of sequence variability in thesegenes. TABLE 5 Genes for Multiplex Type IIS Assay Seq. ID Seq. GeneSequence No Primers ID No. Lipoprotein cctttgagaa agggctctgc ttgagttgta  98-99 5′ 70 Lipase gaaagaaccg ctgcaacaat caatttcatcgctggatgcaatct(Asn291Ser)

ctgggctatg agatca[a

g]taa agtcagagcc gggctatgagatc 3′ aaaagaagca gcaaaatgta 5′ 71caatttcacacagcggatgcttct tttggctctgact 3′ Prothrombin 26731 gaattatttttgtgtttcta aaactatggt 100- 5′ 72 tcccaataaa agtgactctc 101tcagtcacgacgttggatgccaa 26781

agc[g

a]agcctc aatgctccca taaaagtgactctcagc 3′gtgctattca tgggcagctc tctgggctca 5′ 73 cggataacaatttcggatgcactgggagcattgaggc 3′ Factor V taataggact acttctaatc tgtaagagca 102- 5′ 74(Arg506Gln)

gatccctgga caggc[g

a]agga 103 tcagtcacgacgttggatgagca gatccctggacaggc 3′atacaggtat tttgtccttg aagtaacctt tcag 5′ 75 cggataacaatttcggatggacaaaatacctgtattcc 3′ Cholesterol ester 1261 ctcaccatgg gcatttgattgcagagcage 104- 5′ 76 transfer protein

tccgagtcc[g

a] tccagagctt 105 tcagtcacgacgttggatgcaga (CETP) (I405V) gcagctccgagtc3′ 1311 cctgcagtca atgatcaccg ctgtgggcat 5′ 77 ccctgaggtc atgtctcgtacagcggtgatcattggatgcagg aagctctgg 3′ Factor VII 1221 agcaaggactcctgcaaggg ggacagtgga 106- 5′ 78 (R353Q) ggcccacatg ccacccacta 107tcagtcacgacgttggatgccca catgccacccactac 3′ 1271 cc[a

g]gggcacg tggtacctga 5′ 79 cgggcatcgt cagctggggc cagggctgcgcggataacaatttcggatgcccg tcaggtaccacg 3′ Factor XIII 111 caataactctaatgcagcgg aagatgacct 108- 5′ 80 (V34L) gcccacagtg gagcttcagg 109tcagtcacgacgttggatgccca cagtggagcttcag 3′ 161 gc[g

t]tggtgcc ccggggcgtc 5′ 81 aacctgcaag gtatgagcat accccccttcgctcataccttgcaggatgacg 3′ HLA-H exon 2 361 ttgaagctttgggctacgtggatgaccagc 110- 5′ 82 (His63Asp) tgttcgtgtt ctatgat[c

g]at 111 tcagtcacgacgttggatgacca gctgttcgtgttc 3′ 411gagagtcgcc gtgtggagcc ccgaactcca 5′ 83 tgggtttcca gtagaatttctacatggagttcggggatgcaca cggcgactctc 3′ HLA-H exon 4 1021 ggataaccttggctgtaccc cctggggaag 112- 5′ 84 (Cys282Tyr) agcagagata tacgt[g

a]ccag 113 tcagtcacgacgttggatgggga agagcagagatatacgt 3′ 1071gtggagcacc caggcctgga tcagcccctc 5′ 85 attgtgatct gggagccctcgaggggctgatccaggatgggt gctccac 3′ Methylentetra- 761tgaagcactt gaagga gaag gtgtctgcgg 114- 5′ 86 hydrofolate- gag[c

t]cgattt catcatcacg 115 tcagtcacgacgttggatgggga redctaseagagcagagatatacgt 3′ (MTHR) (Ala222Val) 811 cagcttttct ttgaggctgacacattcttc 5′ 87 gaggggctgatccaggatgggt gctccac 3′ P53 Exon4 12101tccagatgaa gctcccagaa 116- 5′ 88 Codon 72 tgccagaggc tgctcccc[g

c]c gtggcccctg 117 gatgaagctcccaggatgccag (Arg72Pro) aggc 3′ 12151caccagcagc tcctacaccg 5′ 89 gcggcccctg gccgccggtgtaggatgctgctg gtgc 3′

[0445] TABLE 6 The mass of Center Fragments for Ten Different SNP Typingby IIS Assay Gene LPL(^(Asn)291^(Ser)) Prothrombin FV(^(Arg)506^(Gln))CETP(^(I)405^(V)) FVII(^(R)353^(Q)) FXIII(^(V)34) Genotype A G G A G A GA G A G T + strand 6213 6229 5845 5829 5677 5661 3388 3372 6128 61125058 5033 mass (Da) − strand 6129 6114 5949 5964 5472 5487 3437 34526174 6189 4916 4940 mass (Da) Gene Hlah2 Hlah4 MTHR(^(Ala)222^(Val))P53exon4(^(Arg)72^(Pro)) Genotype C G G A C T G C + strand 5889 59294392 4376 4400 4415 4586 4546 mass (Da) − strand 5836 5796 4319 43344368 4352 4724 4764 mass (Da)

EXAMPLE 10

[0446] Exemplary use of Parental Medical History Parameter forStratification of Healthy Datebase

[0447] A healthy database can be used to associate a disease state witha specific allele (SNP) that has been found to show a strong associationbetween age and the allele, in particular the homozygous genotype. Themethod involves using the same healthy database used to identify the agedependent association, however stratification is by information given bythe donors about common disorders from which their parents suffered (thedonor's familial history of disease). There are three possible answers adonor could give about the health status of their parents: neither wereaffected, one was affected or both were affected. Only donors above acertain minimum age, depending on the disease, are utilized, as thedonors parents must be old enough to to have exhibited clinical diseasephenotypes. The genotype frequency in each of these groups is determinedand compared with each other. If there is an association of the markerin the donor to a disease the frequency of the heterozyous genotype willbe increased. The frequency of the homozygous genotype should notincrease, as it should be significantly underrepresented in the healthypopulation.

EXAMPLE 11

[0448] Method and Device for Identifying a Biological Sample Description

[0449] A method and device for identifying a biological sample isprovided. Referring now to FIG. 24, an apparatus 10 for identifying abiological sample is disclosed. The apparatus 10 for identifying abiological sample generally comprises a mass spectrometer 15communicating with a computing device 20. In an embodiment, the massspectrometer can be a MALDI-TOF mass spectrometer manufactured byBruker-Franzen Analytik GmbH; however, it will be appreciated that othermass spectrometers can be substituted. The computing device 20 istypically a general purpose computing device. It will be appreciatedthat the computing device could be alternatively configured, forexample, it can be integrated with the mass spectrometer or could bepart of a computer in a larger network system.

[0450] The apparatus 10 for identifying a biological sample can operateas an automated identification system having a robot 25 with a roboticarm 27 configured to deliver a sample plate 29 into a receiving area 31of the mass spectrometer 15. In such a manner, the sample to beidentified can be placed on the plate 29 and automatically received intothe mass spectrometer 15. The biological sample is then processed in themass spectrometer to generate data indicative of the mass of DNAfragments in the biological sample. This data can be sent directly tocomputing device 20, or can have some preprocessing or filteringperformed within the mass spectrometer. In an embodiment, the massspectrometer 15 transmits unprocessed and unfiltered mass spectrometrydata to the computing device 20. It will be appreciated that theanalysis in the computing device can be adjusted to accommodatepreprocessing or filtering performed within the mass spectrometer.

[0451] Referring now to FIG. 25, a general method 35 for identifying abiological sample is shown. In method 35, data are received into acomputing device from a test instrument in block 40. Generally the dataare received in a raw, unprocessed and unfiltered form, butalternatively can have some form of filtering or processing applied. Thetest instrument of an exemplary embodiment is a mass spectrometer asdescribed above. It will be appreciated that other test instrumentscould be substituted for the mass spectrometer.

[0452] The data generated by the test instrument, and in particular themass spectrometer, includes information indicative of the identificationof the biological sample. More specifically, the data are indicative ofthe DNA composition of the biological sample. Typically, massspectrometry data gathered from DNA samples obtained from DNAamplification techniques are noisier than, for example, those fromtypical protein samples. This is due in part because protein samples aremore readily prepared in more abundance, and protein samples are moreeasily ionizable as compared to DNA samples. Accordingly, conventionalmass spectrometer data analysis techniques are generally ineffective forDNA analysis of a biological sample. To improve the analysis capabilityso that DNA composition data can be more readily discerned, anembodiment uses wavelet technology for analyzing the DNA massspectrometry data. Wavelets are an analytical tool for signalprocessing, numerical analysis, and mathematical modeling. Wavelettechnology provides a basic expansion function which is applied to adata set. Using wavelet decomposition, the data set can besimultaneously analyzed in the time and frequency domains. Wavelettransformation is the technique of choice in the analysis of data thatexhibit complicated time (mass) and frequency domain information, suchas MALDI-TOF DNA data. Wavelet transforms as described herein havesuperior denoising properties as compared to conventional Fourieranalysis techniques. Wavelet transformation has proven to beparticularly effective in interpreting the inherently noisy MALDI-TOFspectra of DNA samples. In using wavelets, a “small wave” or “scalingfunction” is used to transform a data set into stages, with each stagerepresenting a frequency component in the data set. Using wavelettransformation, mass spectrometry data can be processed, filtered, andanalyzed with sufficient discrimination to be useful for identificationof the DNA composition for a biological sample.

[0453] Referring again to FIG. 25, the data received in block 40 isdenoised in block 45. The denoised data then has a baseline correctionapplied in block 50. A baseline correction is generally necessary asdata coming from the test instrument, in particular a mass spectrometerinstrument, has data arranged in a generally exponentially decayingmanner. This generally exponential decaying arrangement is not due tothe composition of the biological sample, but is a result of thephysical properties and characteristics of the test instrument, andother chemicals involved in DNA sample preparation. Accordingly,baseline correction substantially corrects the data to remove acomponent of the data attributable to the test system, and samplepreparation characteristics.

[0454] After denoising in block 45 and the baseline correction in block50, a signal remains which is generally indicative of the composition ofthe biological sample. Due to the extraordinary discrimination requiredfor analyzing the DNA composition of the biological sample, thecomposition is not readily apparent from the denoised and correctedsignal. For example, although the signal can include peak areas, it isnot yet clear whether these “putative” peaks actually represent a DNAcomposition, or whether the putative peaks are the result of a systemicor chemical aberration. Further, any call of the composition of thebiological sample would have a probability of error which would beunacceptable for clinical or therapeutic purposes. In such criticalsituations, there needs to be a high degree of certainty that any callor identification of the sample is accurate. Therefore, additional dataprocessing and interpretation is necessary before the sample can beaccurately and confidently identified.

[0455] Since the quantity of data resulting from each mass spectrometrytest is typically thousands of data points, and an automated system canbe set to perform hundreds or even thousands of tests per hour, thequantity of mass spectrometry data generated is enormous. To facilitateefficient transmission and storage of the mass spectrometry data, block55 shows that the denoised and baseline corrected data are compressed.

[0456] In one embodiment, the biological sample is selected andprocessed to have only a limited range of possible compositions.Accordingly, it is therefore known where peaks indicating compositionshould be located, if present. Taking advantage of knowing the locationof these expected peaks, in block 60 the method 35 matches putativepeaks in the processed signal to the location of the expected peaks. Insuch a manner, the probability of each putative peak in the data beingan actual peak indicative of the composition of the biological samplecan be determined. Once the probability of each peak is determined inblock 60, then in block 65 the method 35 statistically determines thecomposition of the biological sample, and determines if confidence ishigh enough to calling a genotype.

[0457] Referring again to block 40, data are received from the testinstrument, which can be a mass spectrometer. In a specificillustration, FIG. 26 shows an example of data from a mass spectrometer.The mass spectrometer data 70 generally comprises data pointsdistributed along an x-axis 71 and a y-axis 72. The x-axis 71 representsthe mass of particles detected, while the y-axis 72 represents anumerical concentration of the particles. As can be seen in FIG. 26, themass spectrometry data 70 is generally exponentially decaying with dataat the left end of the x-axis 73 generally decaying in an exponentialmanner toward data at the heavier end 74 of the x-axis 71. The generalexponential presentation of the data is not indicative of thecomposition of the biological sample, but is more reflective ofsystematic error and characteristics. Further, as described above andillustrated in FIG. 26, considerable noise exists in the massspectrometry DNA data 70.

[0458] Referring again to block 45, where the raw data received in block40 is denoised, the denoising process will be described in more detail.As illustrated in FIG. 25, the denoising process generally entails 1)performing a wavelet transformation on the raw data to decompose the rawdata into wavelet stage coefficients; 2) generating a noise profile fromthe highest stage of wavelet coefficients; and 3) applying a scalednoise profile to other stages in the wavelet transformation. Each stepof the denoising process is further described below.

[0459] Referring now to FIG. 27, the wavelet transformation of the rawmass spectrometry data is generally diagramed. Using wavelettransformation techniques, the mass spectrometry data 70 is sequentiallytransformed into stages. In each stage, the data are represented in ahigh stage and a low stage, with the low stage acting as the input tothe next sequential stage. For example, the mass spectrometry data 70 istransformed into stage 0 high data 82 and stage 0 low data 83. The stage0 low data 83 is then used as an input to the next level transformationto generate stage 1 high data 84 and stage 1 low data 85. In a similarmanner, the stage 1 low data 85 is used as an input to be transformedinto stage 2 high data 86 and stage 2 low data 87. The transformation iscontinued until no more useful information can be derived by furtherwavelet transformation. For example, in the one embodiment a 24-pointwavelet is used. More particularly a wavelet commonly referred to as theDaubechies 24 is used to decompose the raw data. It will be appreciatedthat other wavelets can be used for the wavelet transformation. Sinceeach stage in a wavelet transformation has one-half the data points ofthe previous stage, the wavelet transformation can be continued untilthe stage n low data 89 has around 50 points. Accordingly, the stage nhigh 88 would contain about 100 data points. Since the exemplary waveletis 24 points long, little data or information can be derived bycontinuing the wavelet transformation on a data set of around 50 points.

[0460]FIG. 28 shows an example of stage 0 high data 95. Since stage 0high data 95 is generally indicative of the highest frequencies in themass spectrometry data, stage 0 high data 95 will closely relate to thequantity of high frequency noise in the mass spectrometry data. In FIG.29, an exponential fitting formula has been applied to the stage 0 highdata 95 to generate a stage 0 noise profile 97. In particular, theexponential fitting formula is in the format A₀+A₁ EXP (−A₂ m). It willbe appreciated that other exponential fitting formulae or other types ofcurve fits can be used.

[0461] Referring now to FIG. 30, noise profiles for the other highstages are determined. Since the later data points in each stage willlikely be representative of the level of noise in each stage, only thelater data points in each stage are used to generate a standarddeviation figure that is representative of the noise content in thatparticular stage. More particularly, in generating the noise profile foreach remaining stage, only the last five percent of the data points ineach stage are analyzed to determined a standard deviation number. Itwill be appreciated that other numbers of points, or alternative methodscould be used to generate such a standard deviation figure.

[0462] The standard deviation number for each stage is used with thestage 0 noise profile (the exponential curve) 97 to generate a scalednoise profile for each stage. For example, FIG. 30 shows that stage 1high data 98 has stage 1 high data 103 with the last five percent of thedata points represented by area 99. The points in area 99 are evaluatedto determine a standard deviation number indicative of the noise contentin stage 1 high data 103. The standard deviation number is then usedwith the stage 0 noise profile 97 to generate a stage 1 noise profile.

[0463] In a similar manner, stage 2 high 100 has stage 2 high data 104with the last five percent of points represented by area 101. The datapoints in area 101 are then used to calculate a standard deviationnumber which is then used to scale the stage 0 noise profile 97 togenerate a noise profile for stage 2 data. This same process iscontinued for each of the stage high data as shown by the stage n high105. For stage n high 105, stage n high data 108 has the last fivepercent of data points indicated in area 106. The data points in area106 are used to determine a standard deviation number for stage n. Thestage n standard deviation number is then used with the stage 0 noiseprofile 97 to generate a noise profile for stage n. Accordingly, each ofthe high data stages has a noise profile.

[0464]FIG. 31 shows how the noise profile is applied to the data in eachstage. Generally, the noise profile is used to generate a thresholdwhich is applied to the data in each stage. Since the noise profile isalready scaled to adjust for the noise content of each stage,calculating a threshold permits further adjustment to tune the quantityof noise removed. Wavelet coefficients below the threshold are ignoredwhile those above the threshold are retained. Accordingly, the remainingdata have a substantial portion of the noise content removed.

[0465] Due to the characteristics of wavelet transformation, the lowerstages, such as stage 0 and 1, will have more noise content than thelater stages such as stage 2 or stage n. Indeed, stage n low data arelikely to have little noise at all. Therefore, in an embodiment, thenoise profiles are applied more aggressively in the lower stages andless aggressively in the later stages. For example, FIG. 31 shows thatstage 0 high threshold is determined by multiplying the stage 0 noiseprofile by a factor of four. In such a manner, significant numbers ofdata points in stage 0 high data 95 will be below the threshold andtherefore eliminated. Stage 1 high threshold 112 is set at two times thenoise profile for the stage 1 high data, and stage 2 high threshold 114is set equal to the noise profile for stage 2 high. Following thisgeometric progression, stage n high threshold 116 is thereforedetermined by scaling the noise profile for each respective stage n highby a factor equal to (½^(n-2)). It will be appreciated that otherfactors can be applied to scale the noise profile for each stage. Forexample, the noise profile can be scaled more or less aggressively toaccommodate specific systemic characteristics or sample compositions. Asindicated above, stage n low data does not have a noise profile appliedas stage n low data 118 is assumed to have little or no noise content.After the scaled noise profiles have been applied to each high datastage, the mass spectrometry data 70 has been denoised and is ready forfurther processing. A wavelet transformation of the denoised signalresults in the sparse data set 120 as shown in FIG. 31.

[0466] Referring again to FIG. 25, the mass spectrometry data receivedin block 40 has been denoised in block 45 and is now passed to block 50for baseline correction. Before performing baseline correction, theartifacts introduced by the wavelet transformation procedure can beremoved. Wavelet transformation results vary slightly depending uponwhich point of the wavelet is used as a starting point. For example, anexemplary embodiment uses the 24-point Daubechies-24 wavelet. Bystarting the transformation at the 0 point of the wavelet, a slightlydifferent result will be obtained than if starting at points 1 or 2 ofthe wavelet. Therefore, the denoised data are transformed using everyavailable possible starting point, with the results averaged todetermine a final denoised and shifted signal. For example, FIG. 33shows that the wavelet coefficient is applied 24 different times andthen the results averaged to generate the final data set. It will beappreciated that other techniques can be used to accommodate the slighterror introduced due to wavelet shifting.

[0467] The formula 125 is generally indicated in FIG. 33. Once thesignal has been denoised and shifted, a denoised and shifted signal 130is generated as shown in FIG. 58. FIG. 34 shows an example of thewavelet coefficient 135 data set from the denoised and shifted signal130.

[0468]FIG. 36 shows that putative peak areas 145, 147, and 149 arelocated in the denoised and shifted signal 150. The putative peak areasare systematically identified by taking a moving average along thesignal 150 and identifying sections of the signal 150 which exceed athreshold related to the moving average. It will be appreciated thatother methods can be used to identify putative peak areas in the signal150.

[0469] Putative peak areas 145, 147 and 149 are removed from the signal150 to create a peak-free signal 155 as shown in FIG. 37. The peak-freesignal 155 is further analyzed to identify remaining minimum values 157,and the remaining minimum values 157 are connected to generate thepeak-free signal 155.

[0470]FIG. 38 shows a process of using the peak-free signal 155 togenerate a baseline 170 as shown in FIG. 39. As shown in block 162, awavelet transformation is performed on the peak-free signal 155. All thestages from the wavelet transformation are eliminated in block 164except for the n low stage. The n low stage will generally indicate thelowest frequency component of the peak-free signal 155 and thereforewill generally indicate the system exponential characteristics. Block166 shows that a signal is reconstructed from the n low coefficients andthe baseline signal 170 is generated in block 168.

[0471]FIG. 39 shows a denoised and shifted data signal 172 positionedadjacent a correction baseline 170. The baseline correction 170 issubtracted from the denoised and shifted signal 172 to generate a signal175 having a baseline correction applied as shown in FIG. 40. Althoughsuch a denoised, shifted, and corrected signal is sufficient for mostidentification purposes, the putative peaks in signal 175 are notidentifiable with sufficient accuracy or confidence to call the DNAcomposition of a biological sample.

[0472] Referring again to FIG. 25, the data from the baseline correction50 is now compressed in block 55; the compression technique used in anexemplary embodiment is detailed in FIG. 41. In FIG. 41the data in thebaseline corrected data are presented in an array format 182 with x-axispoints 183 having an associated data value 184. The x-axis is indexed bythe non-zero wavelet coefficients, and the associated value is the valueof the wavelet coefficient. In the illustrated data example in table182, the maximum value 184 is indicated to be 1000. Although aparticularly advantageous compression technique for mass spectrometrydata is shown, it will be appreciated that other compression techniquescan be used. The data also can be stored without compression.

[0473] In compressing the data according to one embodiment, anintermediate format 186 is generated. The intermediate format 186generally comprises a real number having a whole number portion 188 anda decimal portion 190. The whole number portion is the x-axis point 183while the decimal portion is the value data 184 divided by the maximumdata value. For example, in the data 182 a data value “25” is indicatedat x-axis point “100” . The intermediate value for this data point wouldbe “100.025”.

[0474] From the intermediate compressed data 186 the final compresseddata 195 is generated. The first point of the intermediate data filebecomes the starting point for the compressed data. Thereafter each datapoint in the compressed data 195 is calculated as follows: the wholenumber portion (left of the decimal) is replaced by the differencebetween the current and the last whole number. The remainder (right ofthe decimal) remains intact. For example, the starting point of thecompressed data 195 is shown to be the same as the intermediate datapoint which is “100.025”. The comparison between the first intermediatedata point “100.025” and the second intermediate data point “150.220” is“50.220”. Therefore, “50.220” becomes the second point of the compresseddata 195. In a similar manner, the second intermediate point is“150.220” and the third intermediate data point is “500.0001” .Therefore, the third compressed data becomes “350.000”. The calculationfor determining compressed data points is continued until the entirearray of data points is converted to a single array of real numbers.

[0475]FIG. 42 generally describes the method of compressing massspectrometry data, showing that the data file in block 201 is presentedas an array of coefficients in block 202. The data starting point andmaximum is determined as shown in block 203, and the intermediate realnumbers are calculated in block 204 as described above. With theintermediate data points generated, the compressed data are generated inblock 205. The described compression method is highly advantageous andefficient for compressing data sets such as a processed data set from amass spectrometry instrument. The method is particularly useful fordata, such as mass spectrometry data, that uses large numbers and hasbeen processed to have occasional lengthy gaps in x-axis data.Accordingly, an x-y data array for processed mass spectrometry data canbe stored with an effective compression rate of 10×or more. Although thecompression technique is applied to mass spectrometry data, it will beappreciated that the method can also advantageously be applied to otherdata sets.

[0476] Referring again to FIG. 25, peak heights are now determined inblock 60. The first step in determining peak height is illustrated inFIG. 43 where the signal 210 is shifted left or right to correspond withthe position of expected peaks. As the set of possible compositions inthe biological sample is known before the mass spectrometry data aregenerated, the possible positioning of expected peaks is already known.These possible peaks are referred to as expected peaks, such as expectedpeaks 212, 214, and 216. Due to calibration or other errors in the testinstrument data, the entire signal can be shifted left or right from itsactual position, therefore, putative peaks located in the signal, suchas putative peaks 218, 222, and 224 can be compared to the expectedpeaks 212, 214, and 216, respectively. The entire signal is then shiftedsuch that the putative peaks align more closely with the expected peaks.

[0477] Once the putative peaks have been shifted to match expectedpeaks, the strongest putative peak is identified in FIG. 44. In oneembodiment, the strongest peak is calculated as a combination ofanalyzing the overall peak height and area beneath the peak. Forexample, a moderately high but wide peak would be stronger than a veryhigh peak that is extremely narrow. With the strongest putative peakidentified, such as putative peak 225, a Gaussian 228 curve is fit tothe peak 225. Once the Gaussian is fit, the width (W) of the Gaussian isdetermined and will be used as the peak width for future calculations.

[0478] As generally addressed above, the denoised, shifted, andbaseline-corrected signal is not sufficiently processed for confidentlycalling the DNA composition of the biological sample. For example,although the baseline has generally been removed, there are stillresidual baseline effects present. These residual baseline effects aretherefore removed to increase the accuracy and confidence in makingidentifications.

[0479] To remove the residual baseline effects, FIG. 45 shows that theputative peaks 218, 222, and 224 are removed from the baseline correctedsignal. The peaks are removed by identifying a center line 230, 232, and234 of the putative peaks 218, 222, and 224, respectively and removingan area to the left and to the right of the identified center line. Foreach putative peak, an area equal to twice the width (W) of the Gaussianis removed from the left of the center line, while an area equivalent to50 daltons is removed from the right of the center line. It has beenfound that the area representing 50 daltons is adequate to sufficientlyremove the effect of salt adducts which can be associated with an actualpeak. Such adducts appear to the right of an actual peak and are anatural effect from the chemistry involved in acquiring a mass spectrum.Although a 50 Dalton buffer has been selected, it will be appreciatedthat other ranges or methods can be used to reduce or eliminate adducteffects.

[0480] The peaks are removed and remaining minima 247 located as shownin FIG. 46 with the minima 247 connected to create signal 245. A quarticpolynomial is applied to signal 245 to generate a residual baseline 250as shown in FIG. 47. The residual baseline 250 is subtracted from thesignal 225 to generate the final signal 255 as indicated in FIG. 48.Although the residual baseline is the result of a quartic fit to signal245, it will be appreciated that other techniques can be used to smoothor fit the residual baseline.

[0481] To determine peak height, as shown in FIG. 49, a Gaussian such asGaussian 266, 268, and 270 is fit to each of the peaks, such as peaks260, 262, and 264, respectively. Accordingly, the height of the Gaussianis determined as height 272, 274, and 276. Once the height of eachGaussian peak is determined, then the method of identifying a biologicalcompound 35 can move into the genotyping phase 65 as shown in FIG. 25.

[0482] An indication of the confidence that each putative peak is anactual peak can be discerned by calculating a signal-to-noise ratio foreach putative peak. Accordingly, putative peaks with a strongsignal-to-noise ratio are generally more likely to be an actual peakthan a putative peak with a lower signal-to-noise ratio. As describedabove and shown in FIG. 50, the height of each peak, such as height 272,274, and 276, is determined for each peak, with the height being anindicator of signal strength for each peak. The noise profile, such asnoise profile 97, is extrapolated into noise profile 280 across theidentified peaks. At the center line of each of the peaks, a noise valueis determined, such as noise value 282, 283, and 284. With a signalvalues and a noise values generated, signal-to-noise ratios can becalculated for each peak. For example, the signal-to-noise ratio for thefirst peak in FIG. 50 would be calculated as signal value 272 divided bynoise value 282, and in a similar manner the signal-to-noise ratio ofthe middle peak in FIG. 50 would be determined as signal 274 divided bynoise value 283.

[0483] Although the signal-to-noise ratio is generally a usefulindicator of the presence of an actual peak, further processing has beenfound to increase the confidence by which a sample can be identified.For example, the signal-to-noise ratio for each peak in the exemplarlyembodiment can be adjusted by the goodness of fit between a Gaussian andeach putative peak. It is a characteristic of a mass spectrometer thatsample material is detected in a manner that generally complies with anormal distribution. Accordingly, greater confidence will be associatedwith a putative signal having a Gaussian shape than a signal that has aless normal distribution. The error resulting from having a non-Gaussianshape can be referred to as a “residual error”.

[0484] Referring to FIG. 51, a residual error is calculated by taking aroot mean square calculation between the Gaussian 293 and the putativepeak 290 in the data signal. The calculation is performed on data withinone width on either side of a center line of the Gaussian. The residualerror is calculated as:

{square root}[(G−R)²/N],

[0485] where G is the Gaussian signal value, R is the putative peakvalue, and N is the number of points from −W to +W. The calculatedresidual error is used to generate an adjusted signal-to-noise ratio, asdescribed below.

[0486] An adjusted signal noise ratio is calculated for each putativepeak using the formula (S/N) * EXP^((−1·R)), where S/N is thesignal-to-noise ratio, and R is the residual error determined above.Although the exemplary embodiment calculates an adjusted signal-to-noiseratio using a residual error for each peak, it will be appreciated thatother techniques can be used to account for the goodness of fit betweenthe Gaussian and the actual signal.

[0487] Referring now to FIG. 52, a probability is determined that aputative peak is an actual peak. In making the determination of peakprobability, a probability profile 300 is generated where the adjustedsignal-to-noise ratio is the x-axis and the probability is the y-axis.Probability is necessarily in the range between a 0% probability and a100% probability, which is indicated as 1. Generally, the higher theadjusted signal-to-noise ratio, the greater the confidence that aputative peak is an actual peak.

[0488] At some target value for the adjusted signal-to-noise, it hasbeen found that the probability is 100% that the putative peak is anactual peak and can confidently be used to identify the DNA compositionof a biological sample. The target value of adjusted signal-to-noiseratio where the probability is assumed to be 100% is a variableparameter which is to be set according to application specific criteria.For example, the target signal-to-noise ratio will be adjusted dependingupon trial experience, sample characteristics, and the acceptable errortolerance in the overall system. More specifically, for situationsrequiring a conservative approach where error cannot be tolerated, thetarget adjusted signal-to-noise ratio can be set to, for example, 10 andhigher. Accordingly, 100% probability will not be assigned to a peakunless the adjusted signal-to-noise ratio is 10 or over.

[0489] In other situations, a more aggressive approach can be taken assample data is more pronounced or the risk of error can be reduced. Insuch a situation, the system can be set to assume a 100% probabilitywith a 5 or greater target signal-to-noise ratio. Of course, anintermediate signal-to-noise ratio target figure can be selected, suchas 7, when a moderate risk of error can be assumed. Once the targetadjusted signal-to-noise ratio is set for the method, then for anyadjusted signal-to-noise ratio a probability can be determined that aputative peak is an actual peak.

[0490] Due to the chemistry involved in performing an identificationtest, especially a mass spectrometry test of a sample prepared by DNAamplifications, the allelic ratio between the signal strength of thehighest peak and the signal strength of the second (or third and so on)highest peak should fall within an expected ratio. If the allelic ratiofalls outside of normal guidelines, the exemplary embodiment imposes anallelic ratio penalty to the probability. For example, FIG. 53 shows anallelic penalty 315 which has an x-axis 317 that is the ratio betweenthe signal strength of the second highest peak divided by signalstrength of the highest peak. The yaxis 319 assigns a penalty between 0and 1 depending on the determined allelic ratio. In the exemplaryembodiment, it is assumed that allelic ratios over 30% are within theexpected range and therefore no penalty is applied. Between a ratio of10% and 30%, the penalty is linearly increased until at allelic ratiosbelow 10% it is assumed the second-highest peak is not real. For allelicratios between 10% and 30%, the allelic penalty chart 315 is used todetermine a penalty 319, which is multiplied by the peak probabilitydetermined in FIG. 52 to determine a final peak probability. Althoughthe exemplary embodiment incorporates an allelic ratio penalty toaccount for a possible chemistry error, it will be appreciated thatother techniques can be used. Similar treatment will be applied to theother peaks.

[0491] With the peak probability of each peak determined, thestatistical probability for various composition components can bedetermined, as an example, in order to determine the probability of eachof three possible combinations of two peaks,—peak G, peak C andcombinations GG, CC and GC. FIG. 54 shows an example where a mostprobable peak 325 is determined to have a final peak probability of 90%.Peak 325 is positioned such that it represents a G component in thebiological sample. Accordingly, it can be maintained that there is a 90%probability that G exists in the biological sample. Also in the exampleshown in FIG. 54, the second highest probability is peak 330 which has apeak probability of 20%. Peak 330 is at a position associated with a Ccomposition. Accordingly, it can be maintained that there is a 20%probability that C exists in the biological sample.

[0492] With the probability of G existing (90%) and the probability of Cexisting (20%) as a starting point, the probability of combinations of Gand C existing can be calculated. For example, FIG. 54 indicates thatthe probability of GG existing 329 is calculated as 72%. This iscalculated as the probability of GG is equal to the probability of Gexisting (90%) multiplied by the probability of C not existing (100%−20%). So if the probability of G existing is 90% and the probability ofC not existing is 80%, the probability of GG is 72%.

[0493] In a similar manner, the probability of CC existing is equivalentto the probability of C existing (20%) multiplied by the probability ofG not existing (100% −90%). As shown in FIG. 54, the probability of Cexisting is 20% while the probability of G not existing is 10%, sotherefore the probability of CC is only 2%. Finally, the probability ofGC existing is equal to the probability of G existing (90%) multipliedby the probability of C existing (20%). So if the probability of Gexisting is 90% and the probability of C existing is 20%, theprobability of GC existing is 18%. In summary form, then, theprobability of the composition of the biological sample is: probabilityof GG: 72%; probability of GC:     18%; and probability of CC:  2%.

[0494] Once the probabilities of each of the possible combinations hasbeen determined, FIG. 55 is used to decide whether or not sufficientconfidence exists to call the genotype. FIG. 55 shows a call chart 335which has an x-axis 337 which is the ratio of the highest combinationprobability to the second highest combination probability. The yaxis 339simply indicates whether the ratio is sufficiently high to justifycalling the genotype. The value of the ratio can be indicated by M 340.The value of M is set depending upon trial data, sample composition, andthe ability to accept error. For example, the value M can be setrelatively high, such as to a value 4 so that the highest probabilitymust be at least four times greater than the second highest probabilitybefore confidence is established to call a genotype. If a certain levelof error can be acceptable, the value of M can be set to a moreaggressive value, such as to 3, so that the ratio between the highestand second highest probabilities needs to be only a ratio of 3 orhigher. Of course, moderate value can be selected for M when a moderaterisk can be accepted. Using the example of FIG. 54, where theprobability of GG was 72% and the probability of GC was 18%, the ratiobetween 72% and 18% is 4.0, therefore, whether M is set to 3, 3.5, or 4,the system would call the genotype as GG. Although the exemplaryembodiment uses a ratio between the two highest peak probabilities todetermine if a genotype confidently can be called, it will beappreciated that other methods can be substituted. It will also beappreciated that the above techniques can be used for calculatingprobabilities and choosing genotypes (or more general DNA patterns)containing of combinations of more than two peaks.

[0495] Referring now to FIG. 56, a flow chart is shown generallydefining the process of statistically calling genotype described above.In FIG. 56 block 402 shows that the height of each peak is determinedand that in block 404 a noise profile is extrapolated for each peak. Thesignal is determined from the height of each peak in block 406 and thenoise for each peak is determined using the noise profile in block 408.In block 410, the signal-to-noise ratio is calculated for each peak. Toaccount for a non-Gaussian peak shape, a residual error is determined inblock 412 and an adjusted signal-to-noise ratio is calculated in block414. Block 416 shows that a probability profile is developed, with theprobability of each peak existing found in block 418. An allelic penaltycan be applied in block 420, with the allelic penalty applied to theadjusted peak probability in block 422. The probability of eachcombination of components is calculated in block 424 with the ratiobetween the two highest probabilities being determined in block 426. Ifthe ratio of probabilities exceeds a threshold value then the genotypeis called in block 428.

[0496] In another embodiment, the computing device 20 (FIG. 24) supports“standardless” genotyping by identifying data peaks that containputative SNPs. Standardless genotyping is used, for example, whereinsufficient information is known about the samples to determine adistribution of expected peak locations, against which an allelicpenalty as described above can be reliably calculated. This permits thecomputing device to be used for identification of peaks that containputative SNPs from data generated by any assay that fragments a targetedDNA molecule. For such standardless genotyping, peaks that areassociated with an area under the data curve that deviates significantlyfrom the typical area of other peaks in the data spectrum are identifiedand their corresponding mass (location along the x-axis) is determined.

[0497] More particularly, peaks that deviate significantly from theaverage area of other peaks in the data are identified, and the expectedallelic ratio between data peaks is defined in terms of the ratio of thearea under the data peaks. Theoretically, where each genetic loci hasthe same molar concentration of analyte, the area under eachcorresponding peak should be the same, thus producing a 1.0 ratio of thepeak area between any two peaks. In accordance with the methods providedherein, peaks having a smaller ratio relative to the other peaks in thedata will not be recognized as peaks. More particularly, peaks having anarea ratio smaller than 30% relative to a nominal value for peak areawill be assigned an allelic penalty. The mass of the remaining peaks(their location along the x-axis of the data) will be determined basedon oligonucleotide standards.

[0498]FIG. 57 shows a flow diagram representation of the processing bythe computing device 20 (FIG. 24) when performing standardlessgenotyping. In the first operation, represented by the flow diagram boxnumbered 502, the computing device receives data from the massspectrometer. Next, the height of each putative peak in the data sampleis determined, as indicated by the block 504. After the height of eachpeak in the mass spectrometer data is determined, a de-noise process 505is performed, beginning with an extrapolation of the noise profile(block 506), followed by finding the noise of each peak (block 508) andcalculating the signal to noise ratio for each data sample (block 510).Each of these operations can be performed in accordance with thedescription above for denoise operations 45 of FIG. 25. Other suitabledenoise operations will occur to those skilled in the art.

[0499] The next operation is to find the residual error associated witheach data point. This is represented by the block 512 in FIG. 57. Thenext step, block 514, involves calculating an adjusted signal to noiseratio for each identified peak. A probability profile is developed next(block 516), followed by a determination of the peak probabilities atblock 518. In an exemplary embodiment, the denoise operations of FIG.57, comprising block 502 to block 518, comprise the correspondingoperations described above in conjunction with FIG. 56 for block 402through block 418, respectively.

[0500] The next action for the standardless genotype processing is todetermine an allelic penalty for each peak, indicated by the block 524.As noted above, the standardless genotype processing of FIG. 57determines an allelic penalty by comparing area under the peaks.Therefore, rather than compare signal strength ratios to determine anallelic penalty, such as described above for FIG. 53, the standardlessprocessing determines the area under each of the identified peaks andcompares the ratio of those areas. Determining the area under each peakcan be computed using conventional numerical analysis techniques forcalculating the area under a curve for experimental data.

[0501] Thus, the allelic penalty is assigned in accordance with FIG. 58,which shows that no penalty is assigned to peaks having a peak arearelative to an expected average area value that is greater than 0.30(30%). The allelic penalty is applied to the peak probability value,which can be determined according to the process such as described inFIG. 52. It should be apparent from FIG. 58 that the allelic penaltyimposed for peaks below a ratio of 30% is that such peaks will beremoved from further measurement and processing. Other penalty schemes,however, can be imposed in accordance with knowledge about the databeing processed, as determined by those skilled in the art.

[0502] After the allelic penalty has been determined and applied, thestandardless genotype processing compares the location of the remainingputative peaks to oligonucleotide standards to determine correspondingmasses in the processing for block 524. For standardless genotype data,the processing of the block 524 is performed to determine mass andgenotype, rather than performing the operations corresponding to block424, 426, and 428 of FIG. 33. Techniques for performing such comparisonsand determining mass will be known to those skilled in the art.

[0503] In another embodiment, the computing device 20 (FIG. 24) permitsthe detection and determination of the mass (location along the x-axisof the data) of the sense and antisense strand of fragments generated inthe assay. If desired, the computing device can also detect anddetermine the quantity (area under each peak) of the respective senseand antisense strands, using a similar technique to that described abovefor standardless genotype processing. The data generated for each typeof strand can then be combined to achieve a data redundancy and tothereby increase the confidence level of the determined genotype. Thistechnique obviates primer peaks that are often observed in data fromother diagnostic methods, thereby permitting a higher level ofmultiplexing. In addition, when quantitation is used in poolingexperiments, the ratio of the measured peak areas is more reliablycalculated than the peak identifying technique, due to data redundancy.

[0504]FIG. 23 is a flow diagram that illustrates the processingimplemented by the computing device 20 to perform sense and antisenseprocessing. In the first operation, represented by the flow diagram boxnumbered 602, the computing device receives data from the massspectrometer. This data will include data for the sense strand andantisense strand of assay fragments. Next, the height of each putativepeak in the data sample is determined, as indicated by the block 604.After the height of each peak in the mass spectrometer data isdetermined, a de-noise process 605 is performed, beginning with anoperation that extrapolates the noise profile (block 606), followed byfinding the noise of each peak (block 608) and calculating the signal tonoise ratio for each data sample (block 610). Each of these operationscan be performed in accordance with the description above for thedenoise operations 45 of FIG. 25. Other suitable denoise operations willoccur to those skilled in the art. The next operation is to find theresidual error associated with each data point. This is represented bythe block 612 in FIG. 36.

[0505] After the residual error for the data of the sense strand andantisense strand has been performed, processing to identify thegenotypes will be performed for the sense strand and also for theantisense strand. Therefore, FIG. 23 shows that processing includessense strand processing (block 630) and antisense strand processing(block 640). Each block 630, 640 includes processing that corresponds toadjusting the signal to noise ratio, developing a probability profile,determining an allelic penalty, adjusting the peak probability by theallelic penalty, calculating genotype probabilities, and testinggenotype probability ratios, such as described above in conjunction withblocks 414 through 426 of FIG. 56. The processing of each block 630, 640can, if desired, include standardless processing operations such asdescribed above in conjunction with FIG. 57. The standardless processingcan be included in place of or in addition to the processing operationsof FIG. 56.

[0506] After the genotype probability processing is completed, the datafrom the sense strand and antisense strand processing is combined andcompared to expected database values to obtain the benefits of dataredundancy as between the sense strand and antisense strand. Thoseskilled in the art will understand techniques to take advantage of knowndata redundancies between a sense strand and antisense strand of assayfragments. This processing is represented by the block 650. After thedata from the two strands is combined for processing, the genotypeprocessing is performed (block 660) and the genotype is identified.

[0507] Since modifications will be apparent to those of skill in thisart, it is intended that this invention be limited only by the scope ofthe appended claims.

0 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 118 <210> SEQ ID NO 1<211> LENGTH: 361 <212> TYPE: DNA <213> ORGANISM: Homo Sapien <400>SEQUENCE: 1 ctgaggacct ggtcctctga ctgctctttt cacccatcta cagtcccccttgccgtccca 60 agcaatggat gatttgatgc tgtccccgga cgatattgaa caatggttcactgaagaccc 120 aggtccagat gaagctccca gaatgccaga ggctgctccc cgcgtggcccctgcaccagc 180 agctcctaca ccggcggccc ctgcaccagc cccctcctgg cccctgtcatcttctgtccc 240 ttcccagaaa acctaccagg gcagctacgg tttccgtctg ggcttcttgcattctgggac 300 agccaagtct gtgacttgca cggtcagttg ccctgagggg ctggcttccatgagacttca 360 a 361 <210> SEQ ID NO 2 <211> LENGTH: 44 <212> TYPE: DNA<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide Primer <400> SEQUENCE: 2 cccagtcacgacgttgtaaa acgctgagga cctggtcctc tgac 44 <210> SEQ ID NO 3 <211> LENGTH:42 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Oligonucleotide Primer <400> SEQUENCE: 3agcggataac aatttcacac aggttgaagt ctcatggaag cc 42 <210> SEQ ID NO 4<211> LENGTH: 17 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE: 4gccagaggct gctcccc 17 <210> SEQ ID NO 5 <211> LENGTH: 17 <212> TYPE: DNA<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Probe <400> SEQUENCE: 5 gccagaggct gctcccc 17 <210> SEQ IDNO 6 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE: 6gccagaggct gctccccgc 19 <210> SEQ ID NO 7 <211> LENGTH: 18 <212> TYPE:DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Probe <400> SEQUENCE: 7 gccagaggct gctccccc 18 <210> SEQ IDNO 8 <211> LENGTH: 161 <212> TYPE: DNA <213> ORGANISM: Homo Sapien <400>SEQUENCE: 8 gtccgtcaga acccatgcgg cagcaaggcc tgccgccgcc tcttcggcccagtggacagc 60 gagcagctga gccgcgactg tgatgcgcta atggcgggct gcatccaggaggcccgtgag 120 cgatggaact tcgactttgt caccgagaca ccactggagg g 161 <210>SEQ ID NO 9 <211> LENGTH: 43 <212> TYPE: DNA <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Oligonucleotide Primer<400> SEQUENCE: 9 cccagtcacg acgttgtaaa acggtccgtc agaacccatg cgg 43<210> SEQ ID NO 10 <211> LENGTH: 44 <212> TYPE: DNA <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Oligonucleotide Primer <400> SEQUENCE: 10 agcggataac aatttcacacaggctccagt ggtgtctcgg tgac 44 <210> SEQ ID NO 11 <211> LENGTH: 15 <212>TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide Primer <400> SEQUENCE: 11 cagcgagcag ctgag15 <210> SEQ ID NO 12 <211> LENGTH: 15 <212> TYPE: DNA <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400>SEQUENCE: 12 cagcgagcag ctgag 15 <210> SEQ ID NO 13 <211> LENGTH: 16<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Probe <400> SEQUENCE: 13 cagcgagcag ctgagc 16 <210>SEQ ID NO 14 <211> LENGTH: 17 <212> TYPE: DNA <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400> SEQUENCE:14 cagcgagcag ctgagac 17 <210> SEQ ID NO 15 <211> LENGTH: 205 <212>TYPE: DNA <213> ORGANISM: Homo Sapien <400> SEQUENCE: 15 gcgctccattcatctcttca tcgactctct gttgaatgaa gaaaatccaa gtaaggccta 60 caggtgcagttccaaggaag cctttgagaa agggctctgc ttgagttgta gaaagaaccg 120 ctgcaacaatctgggctatg agatcaataa agtcagagcc aaaagaagca gcaaaatgta 180 cctgaagactcgttctcaga tgccc 205 <210> SEQ ID NO 16 <211> LENGTH: 42 <212> TYPE: DNA<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide Primers <400> SEQUENCE: 16 cccagtcacgacgttgtaaa acggcgctcc attcatctct tc 42 <210> SEQ ID NO 17 <211> LENGTH:42 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Oligonucleotide Primer <400> SEQUENCE: 17agcggataac aatttcacac agggggcatc tgagaacgag tc 42 <210> SEQ ID NO 18<211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Oligonucleotide Primer <400>SEQUENCE: 18 caatctgggc tatgagatca 20 <210> SEQ ID NO 19 <211> LENGTH:20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Probe <400> SEQUENCE: 19 caatctgggc tatgagatca20 <210> SEQ ID NO 20 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400>SEQUENCE: 20 caatctgggc tatgagatca a 21 <210> SEQ ID NO 21 <211> LENGTH:22 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Probe <400> SEQUENCE: 21 caatctgggc tatgagatcagt 22 <210> SEQ ID NO 22 <211> LENGTH: 60 <212> TYPE: DNA <213>ORGANISM: Homo Sapien <220> FEATURE: <223> OTHER INFORMATION: Probe<400> SEQUENCE: 22 gtgccggcta ctcggatggc agcaaggact cctgcaagggggacagtgga ggcccacatg 60 <210> SEQ ID NO 23 <211> LENGTH: 60 <212> TYPE:DNA <213> ORGANISM: Homo sapien <400> SEQUENCE: 23 ccacccacta ccggggcacgtggtacctga cgggcatcgt cagctggggc cagggctgcg 60 <210> SEQ ID NO 24 <211>LENGTH: 42 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE:24 cccagtcacg acgttgtaaa acgatggcag caaggactcc tg 42 <210> SEQ ID NO 25<211> LENGTH: 18 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Oligonucleotide primer <400>SEQUENCE: 25 cacatgccac ccactacc 18 <210> SEQ ID NO 26 <211> LENGTH: 43<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 26 agcggataacaatttcacac aggtgacgat gcccgtcagg tac 43 <210> SEQ ID NO 27 <211> LENGTH:15 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Probe <400> SEQUENCE: 27 atgccaccca ctacc 15<210> SEQ ID NO 28 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400>SEQUENCE: 28 cacatgccac ccactaccg 19 <210> SEQ ID NO 29 <211> LENGTH: 20<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Probe <400> SEQUENCE: 29 cacatgccac ccactaccag 20<210> SEQ ID NO 30 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Probe <400>SEQUENCE: 30 agcggataac aatttcacac agg 23 <210> SEQ ID NO 31 <211>LENGTH: 2363 <212> TYPE: DNA <213> ORGANISM: Homo Sapien <220> FEATURE:<221> NAME/KEY: CDS <222> LOCATION: (138)...(2126) <223> OTHERINFORMATION: AKAP-10 <300> PUBLICATION INFORMATION: <308> DATABASEACCESSION NUMBER: GenBank AF037439 <309> DATABASE ENTRY DATE: 1997-12-21<400> SEQUENCE: 31 gcggcttgtt gataatatgg cggctggagc tgcctgggcatcccgaggag gcggtggggc 60 ccactcccgg aagaagggtc ccttttcgcg ctagtgcagcggcccctctg gacccggaag 120 tccgggccgg ttgctga atg agg gga gcc ggg ccc tccccg cgc cag tcc 170 Met Arg Gly Ala Gly Pro Ser Pro Arg Gln Ser 1 5 10ccc cgc acc ctc cgt ccc gac ccg ggc ccc gcc atg tcc ttc ttc cgg 218 ProArg Thr Leu Arg Pro Asp Pro Gly Pro Ala Met Ser Phe Phe Arg 15 20 25 cggaaa gtg aaa ggc aaa gaa caa gag aag acc tca gat gtg aag tcc 266 Arg LysVal Lys Gly Lys Glu Gln Glu Lys Thr Ser Asp Val Lys Ser 30 35 40 att aaagct tca ata tcc gta cat tcc cca caa aaa agc act aaa aat 314 Ile Lys AlaSer Ile Ser Val His Ser Pro Gln Lys Ser Thr Lys Asn 45 50 55 cat gcc ttgctg gag gct gca gga cca agt cat gtt gca atc aat gcc 362 His Ala Leu LeuGlu Ala Ala Gly Pro Ser His Val Ala Ile Asn Ala 60 65 70 75 att tct gccaac atg gac tcc ttt tca agt agc agg aca gcc aca ctt 410 Ile Ser Ala AsnMet Asp Ser Phe Ser Ser Ser Arg Thr Ala Thr Leu 80 85 90 aag aag cag ccaagc cac atg gag gct gct cat ttt ggt gac ctg ggc 458 Lys Lys Gln Pro SerHis Met Glu Ala Ala His Phe Gly Asp Leu Gly 95 100 105 aga tct tgt ctggac tac cag act caa gag acc aaa tca agc ctt tct 506 Arg Ser Cys Leu AspTyr Gln Thr Gln Glu Thr Lys Ser Ser Leu Ser 110 115 120 aag acc ctt gaacaa gtc ttg cac gac act att gtc ctc cct tac ttc 554 Lys Thr Leu Glu GlnVal Leu His Asp Thr Ile Val Leu Pro Tyr Phe 125 130 135 att caa ttc atggaa ctt cgg cga atg gag cat ttg gtg aaa ttt tgg 602 Ile Gln Phe Met GluLeu Arg Arg Met Glu His Leu Val Lys Phe Trp 140 145 150 155 tta gag gctgaa agt ttt cat tca aca act tgg tcg cga ata aga gca 650 Leu Glu Ala GluSer Phe His Ser Thr Thr Trp Ser Arg Ile Arg Ala 160 165 170 cac agt ctaaac aca atg aag cag agc tca ctg gct gag cct gtc tct 698 His Ser Leu AsnThr Met Lys Gln Ser Ser Leu Ala Glu Pro Val Ser 175 180 185 cca tct aaaaag cat gaa act aca gcg tct ttt tta act gat tct ctt 746 Pro Ser Lys LysHis Glu Thr Thr Ala Ser Phe Leu Thr Asp Ser Leu 190 195 200 gat aag agattg gag gat tct ggc tca gca cag ttg ttt atg act cat 794 Asp Lys Arg LeuGlu Asp Ser Gly Ser Ala Gln Leu Phe Met Thr His 205 210 215 tca gaa ggaatt gac ctg aat aat aga act aac agc act cag aat cac 842 Ser Glu Gly IleAsp Leu Asn Asn Arg Thr Asn Ser Thr Gln Asn His 220 225 230 235 ttg ctgctt tcc cag gaa tgt gac agt gcc cat tct ctc cgt ctt gaa 890 Leu Leu LeuSer Gln Glu Cys Asp Ser Ala His Ser Leu Arg Leu Glu 240 245 250 atg gccaga gca gga act cac caa gtt tcc atg gaa acc caa gaa tct 938 Met Ala ArgAla Gly Thr His Gln Val Ser Met Glu Thr Gln Glu Ser 255 260 265 tcc tctaca ctt aca gta gcc agt aga aat agt ccc gct tct cca cta 986 Ser Ser ThrLeu Thr Val Ala Ser Arg Asn Ser Pro Ala Ser Pro Leu 270 275 280 aaa gaattg tca gga aaa cta atg aaa agt ata gaa caa gat gca gtg 1034 Lys Glu LeuSer Gly Lys Leu Met Lys Ser Ile Glu Gln Asp Ala Val 285 290 295 aat actttt acc aaa tat ata tct cca gat gct gct aaa cca ata cca 1082 Asn Thr PheThr Lys Tyr Ile Ser Pro Asp Ala Ala Lys Pro Ile Pro 300 305 310 315 attaca gaa gca atg aga aat gac atc ata gca agg att tgt gga gaa 1130 Ile ThrGlu Ala Met Arg Asn Asp Ile Ile Ala Arg Ile Cys Gly Glu 320 325 330 gatgga cag gtg gat ccc aac tgt ttc gtt ttg gca cag tcc ata gtc 1178 Asp GlyGln Val Asp Pro Asn Cys Phe Val Leu Ala Gln Ser Ile Val 335 340 345 tttagt gca atg gag caa gag cac ttt agt gag ttt ctg cga agt cac 1226 Phe SerAla Met Glu Gln Glu His Phe Ser Glu Phe Leu Arg Ser His 350 355 360 catttc tgt aaa tac cag att gaa gtg ctg acc agt gga act gtt tac 1274 His PheCys Lys Tyr Gln Ile Glu Val Leu Thr Ser Gly Thr Val Tyr 365 370 375 ctggct gac att ctc ttc tgt gag tca gcc ctc ttt tat ttc tct gag 1322 Leu AlaAsp Ile Leu Phe Cys Glu Ser Ala Leu Phe Tyr Phe Ser Glu 380 385 390 395tac atg gaa aaa gag gat gca gtg aat atc tta caa ttc tgg ttg gca 1370 TyrMet Glu Lys Glu Asp Ala Val Asn Ile Leu Gln Phe Trp Leu Ala 400 405 410gca gat aac ttc cag tct cag ctt gct gcc aaa aag ggg caa tat gat 1418 AlaAsp Asn Phe Gln Ser Gln Leu Ala Ala Lys Lys Gly Gln Tyr Asp 415 420 425gga cag gag gca cag aat gat gcc atg att tta tat gac aag tac ttc 1466 GlyGln Glu Ala Gln Asn Asp Ala Met Ile Leu Tyr Asp Lys Tyr Phe 430 435 440tcc ctc caa gcc aca cat cct ctt gga ttt gat gat gtt gta cga tta 1514 SerLeu Gln Ala Thr His Pro Leu Gly Phe Asp Asp Val Val Arg Leu 445 450 455gaa att gaa tcc aat atc tgc agg gaa ggt ggg cca ctc ccc aac tgt 1562 GluIle Glu Ser Asn Ile Cys Arg Glu Gly Gly Pro Leu Pro Asn Cys 460 465 470475 ttc aca act cca tta cgt cag gcc tgg aca acc atg gag aag gtc ttt 1610Phe Thr Thr Pro Leu Arg Gln Ala Trp Thr Thr Met Glu Lys Val Phe 480 485490 ttg cct ggc ttt ctg tcc agc aat ctt tat tat aaa tat ttg aat gat 1658Leu Pro Gly Phe Leu Ser Ser Asn Leu Tyr Tyr Lys Tyr Leu Asn Asp 495 500505 ctc atc cat tcg gtt cga gga gat gaa ttt ctg ggc ggg aac gtg tcg 1706Leu Ile His Ser Val Arg Gly Asp Glu Phe Leu Gly Gly Asn Val Ser 510 515520 ccg act gct cct ggc tct gtt ggc cct cct gat gag tct cac cca ggg 1754Pro Thr Ala Pro Gly Ser Val Gly Pro Pro Asp Glu Ser His Pro Gly 525 530535 agt tct gac agc tct gcg tct cag tcc agt gtg aaa aaa gcc agt att 1802Ser Ser Asp Ser Ser Ala Ser Gln Ser Ser Val Lys Lys Ala Ser Ile 540 545550 555 aaa ata ctg aaa aat ttt gat gaa gcg ata att gtg gat gcg gca agt1850 Lys Ile Leu Lys Asn Phe Asp Glu Ala Ile Ile Val Asp Ala Ala Ser 560565 570 ctg gat cca gaa tct tta tat caa cgg aca tat gcc ggg aag atg aca1898 Leu Asp Pro Glu Ser Leu Tyr Gln Arg Thr Tyr Ala Gly Lys Met Thr 575580 585 ttt gga aga gtg agt gac ttg ggg caa ttc atc cgg gaa tct gag cct1946 Phe Gly Arg Val Ser Asp Leu Gly Gln Phe Ile Arg Glu Ser Glu Pro 590595 600 gaa cct gat gta agg aaa tca aaa gga tcc atg ttc tca caa gct atg1994 Glu Pro Asp Val Arg Lys Ser Lys Gly Ser Met Phe Ser Gln Ala Met 605610 615 aag aaa tgg gtg caa gga aat act gat gag gcc cag gaa gag cta gct2042 Lys Lys Trp Val Gln Gly Asn Thr Asp Glu Ala Gln Glu Glu Leu Ala 620625 630 635 tgg aag att gct aaa atg ata gtc agt gac att atg cag cag gctcag 2090 Trp Lys Ile Ala Lys Met Ile Val Ser Asp Ile Met Gln Gln Ala Gln640 645 650 tat gat caa ccg tta gag aaa tct aca aag tta tga ctcaaaactt2136 Tyr Asp Gln Pro Leu Glu Lys Ser Thr Lys Leu * 655 660 gagataaaggaaatctgctt gtgaaaaata agagaacttt tttcccttgg ttggattctt 2196 caacacagccaatgaaaaca gcactatatt tctgatctgt cactgttgtt tccagggaga 2256 gaatggggagacaatcctag gacttccacc ctaatgcagt tacctgtagg gcataattgg 2316 atggcacatgatgtttcaca cagtgaggag tctttaaagg ttaccaa 2363 <210> SEQ ID NO 32 <211>LENGTH: 662 <212> TYPE: PRT <213> ORGANISM: Homo Sapien <400> SEQUENCE:32 Met Arg Gly Ala Gly Pro Ser Pro Arg Gln Ser Pro Arg Thr Leu Arg 1 510 15 Pro Asp Pro Gly Pro Ala Met Ser Phe Phe Arg Arg Lys Val Lys Gly 2025 30 Lys Glu Gln Glu Lys Thr Ser Asp Val Lys Ser Ile Lys Ala Ser Ile 3540 45 Ser Val His Ser Pro Gln Lys Ser Thr Lys Asn His Ala Leu Leu Glu 5055 60 Ala Ala Gly Pro Ser His Val Ala Ile Asn Ala Ile Ser Ala Asn Met 6570 75 80 Asp Ser Phe Ser Ser Ser Arg Thr Ala Thr Leu Lys Lys Gln Pro Ser85 90 95 His Met Glu Ala Ala His Phe Gly Asp Leu Gly Arg Ser Cys Leu Asp100 105 110 Tyr Gln Thr Gln Glu Thr Lys Ser Ser Leu Ser Lys Thr Leu GluGln 115 120 125 Val Leu His Asp Thr Ile Val Leu Pro Tyr Phe Ile Gln PheMet Glu 130 135 140 Leu Arg Arg Met Glu His Leu Val Lys Phe Trp Leu GluAla Glu Ser 145 150 155 160 Phe His Ser Thr Thr Trp Ser Arg Ile Arg AlaHis Ser Leu Asn Thr 165 170 175 Met Lys Gln Ser Ser Leu Ala Glu Pro ValSer Pro Ser Lys Lys His 180 185 190 Glu Thr Thr Ala Ser Phe Leu Thr AspSer Leu Asp Lys Arg Leu Glu 195 200 205 Asp Ser Gly Ser Ala Gln Leu PheMet Thr His Ser Glu Gly Ile Asp 210 215 220 Leu Asn Asn Arg Thr Asn SerThr Gln Asn His Leu Leu Leu Ser Gln 225 230 235 240 Glu Cys Asp Ser AlaHis Ser Leu Arg Leu Glu Met Ala Arg Ala Gly 245 250 255 Thr His Gln ValSer Met Glu Thr Gln Glu Ser Ser Ser Thr Leu Thr 260 265 270 Val Ala SerArg Asn Ser Pro Ala Ser Pro Leu Lys Glu Leu Ser Gly 275 280 285 Lys LeuMet Lys Ser Ile Glu Gln Asp Ala Val Asn Thr Phe Thr Lys 290 295 300 TyrIle Ser Pro Asp Ala Ala Lys Pro Ile Pro Ile Thr Glu Ala Met 305 310 315320 Arg Asn Asp Ile Ile Ala Arg Ile Cys Gly Glu Asp Gly Gln Val Asp 325330 335 Pro Asn Cys Phe Val Leu Ala Gln Ser Ile Val Phe Ser Ala Met Glu340 345 350 Gln Glu His Phe Ser Glu Phe Leu Arg Ser His His Phe Cys LysTyr 355 360 365 Gln Ile Glu Val Leu Thr Ser Gly Thr Val Tyr Leu Ala AspIle Leu 370 375 380 Phe Cys Glu Ser Ala Leu Phe Tyr Phe Ser Glu Tyr MetGlu Lys Glu 385 390 395 400 Asp Ala Val Asn Ile Leu Gln Phe Trp Leu AlaAla Asp Asn Phe Gln 405 410 415 Ser Gln Leu Ala Ala Lys Lys Gly Gln TyrAsp Gly Gln Glu Ala Gln 420 425 430 Asn Asp Ala Met Ile Leu Tyr Asp LysTyr Phe Ser Leu Gln Ala Thr 435 440 445 His Pro Leu Gly Phe Asp Asp ValVal Arg Leu Glu Ile Glu Ser Asn 450 455 460 Ile Cys Arg Glu Gly Gly ProLeu Pro Asn Cys Phe Thr Thr Pro Leu 465 470 475 480 Arg Gln Ala Trp ThrThr Met Glu Lys Val Phe Leu Pro Gly Phe Leu 485 490 495 Ser Ser Asn LeuTyr Tyr Lys Tyr Leu Asn Asp Leu Ile His Ser Val 500 505 510 Arg Gly AspGlu Phe Leu Gly Gly Asn Val Ser Pro Thr Ala Pro Gly 515 520 525 Ser ValGly Pro Pro Asp Glu Ser His Pro Gly Ser Ser Asp Ser Ser 530 535 540 AlaSer Gln Ser Ser Val Lys Lys Ala Ser Ile Lys Ile Leu Lys Asn 545 550 555560 Phe Asp Glu Ala Ile Ile Val Asp Ala Ala Ser Leu Asp Pro Glu Ser 565570 575 Leu Tyr Gln Arg Thr Tyr Ala Gly Lys Met Thr Phe Gly Arg Val Ser580 585 590 Asp Leu Gly Gln Phe Ile Arg Glu Ser Glu Pro Glu Pro Asp ValArg 595 600 605 Lys Ser Lys Gly Ser Met Phe Ser Gln Ala Met Lys Lys TrpVal Gln 610 615 620 Gly Asn Thr Asp Glu Ala Gln Glu Glu Leu Ala Trp LysIle Ala Lys 625 630 635 640 Met Ile Val Ser Asp Ile Met Gln Gln Ala GlnTyr Asp Gln Pro Leu 645 650 655 Glu Lys Ser Thr Lys Leu 660 <210> SEQ IDNO 33 <211> LENGTH: 2363 <212> TYPE: DNA <213> ORGANISM: Homo Sapien<220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (138)...(2126) <223>OTHER INFORMATION: AKAP-10-5 <220> FEATURE: <221> NAME/KEY: allele <222>LOCATION: 2073 <223> OTHER INFORMATION: Single Nucleotide Polymorphism:A to G <400> SEQUENCE: 33 gcggcttgtt gataatatgg cggctggagc tgcctgggcatcccgaggag gcggtggggc 60 ccactcccgg aagaagggtc ccttttcgcg ctagtgcagcggcccctctg gacccggaag 120 tccgggccgg ttgctga atg agg gga gcc ggg ccc tccccg cgc cag tcc 170 Met Arg Gly Ala Gly Pro Ser Pro Arg Gln Ser 1 5 10ccc cgc acc ctc cgt ccc gac ccg ggc ccc gcc atg tcc ttc ttc cgg 218 ProArg Thr Leu Arg Pro Asp Pro Gly Pro Ala Met Ser Phe Phe Arg 15 20 25 cggaaa gtg aaa ggc aaa gaa caa gag aag acc tca gat gtg aag tcc 266 Arg LysVal Lys Gly Lys Glu Gln Glu Lys Thr Ser Asp Val Lys Ser 30 35 40 att aaagct tca ata tcc gta cat tcc cca caa aaa agc act aaa aat 314 Ile Lys AlaSer Ile Ser Val His Ser Pro Gln Lys Ser Thr Lys Asn 45 50 55 cat gcc ttgctg gag gct gca gga cca agt cat gtt gca atc aat gcc 362 His Ala Leu LeuGlu Ala Ala Gly Pro Ser His Val Ala Ile Asn Ala 60 65 70 75 att tct gccaac atg gac tcc ttt tca agt agc agg aca gcc aca ctt 410 Ile Ser Ala AsnMet Asp Ser Phe Ser Ser Ser Arg Thr Ala Thr Leu 80 85 90 aag aag cag ccaagc cac atg gag gct gct cat ttt ggt gac ctg ggc 458 Lys Lys Gln Pro SerHis Met Glu Ala Ala His Phe Gly Asp Leu Gly 95 100 105 aga tct tgt ctggac tac cag act caa gag acc aaa tca agc ctt tct 506 Arg Ser Cys Leu AspTyr Gln Thr Gln Glu Thr Lys Ser Ser Leu Ser 110 115 120 aag acc ctt gaacaa gtc ttg cac gac act att gtc ctc cct tac ttc 554 Lys Thr Leu Glu GlnVal Leu His Asp Thr Ile Val Leu Pro Tyr Phe 125 130 135 att caa ttc atggaa ctt cgg cga atg gag cat ttg gtg aaa ttt tgg 602 Ile Gln Phe Met GluLeu Arg Arg Met Glu His Leu Val Lys Phe Trp 140 145 150 155 tta gag gctgaa agt ttt cat tca aca act tgg tcg cga ata aga gca 650 Leu Glu Ala GluSer Phe His Ser Thr Thr Trp Ser Arg Ile Arg Ala 160 165 170 cac agt ctaaac aca atg aag cag agc tca ctg gct gag cct gtc tct 698 His Ser Leu AsnThr Met Lys Gln Ser Ser Leu Ala Glu Pro Val Ser 175 180 185 cca tct aaaaag cat gaa act aca gcg tct ttt tta act gat tct ctt 746 Pro Ser Lys LysHis Glu Thr Thr Ala Ser Phe Leu Thr Asp Ser Leu 190 195 200 gat aag agattg gag gat tct ggc tca gca cag ttg ttt atg act cat 794 Asp Lys Arg LeuGlu Asp Ser Gly Ser Ala Gln Leu Phe Met Thr His 205 210 215 tca gaa ggaatt gac ctg aat aat aga act aac agc act cag aat cac 842 Ser Glu Gly IleAsp Leu Asn Asn Arg Thr Asn Ser Thr Gln Asn His 220 225 230 235 ttg ctgctt tcc cag gaa tgt gac agt gcc cat tct ctc cgt ctt gaa 890 Leu Leu LeuSer Gln Glu Cys Asp Ser Ala His Ser Leu Arg Leu Glu 240 245 250 atg gccaga gca gga act cac caa gtt tcc atg gaa acc caa gaa tct 938 Met Ala ArgAla Gly Thr His Gln Val Ser Met Glu Thr Gln Glu Ser 255 260 265 tcc tctaca ctt aca gta gcc agt aga aat agt ccc gct tct cca cta 986 Ser Ser ThrLeu Thr Val Ala Ser Arg Asn Ser Pro Ala Ser Pro Leu 270 275 280 aaa gaattg tca gga aaa cta atg aaa agt ata gaa caa gat gca gtg 1034 Lys Glu LeuSer Gly Lys Leu Met Lys Ser Ile Glu Gln Asp Ala Val 285 290 295 aat actttt acc aaa tat ata tct cca gat gct gct aaa cca ata cca 1082 Asn Thr PheThr Lys Tyr Ile Ser Pro Asp Ala Ala Lys Pro Ile Pro 300 305 310 315 attaca gaa gca atg aga aat gac atc ata gca agg att tgt gga gaa 1130 Ile ThrGlu Ala Met Arg Asn Asp Ile Ile Ala Arg Ile Cys Gly Glu 320 325 330 gatgga cag gtg gat ccc aac tgt ttc gtt ttg gca cag tcc ata gtc 1178 Asp GlyGln Val Asp Pro Asn Cys Phe Val Leu Ala Gln Ser Ile Val 335 340 345 tttagt gca atg gag caa gag cac ttt agt gag ttt ctg cga agt cac 1226 Phe SerAla Met Glu Gln Glu His Phe Ser Glu Phe Leu Arg Ser His 350 355 360 catttc tgt aaa tac cag att gaa gtg ctg acc agt gga act gtt tac 1274 His PheCys Lys Tyr Gln Ile Glu Val Leu Thr Ser Gly Thr Val Tyr 365 370 375 ctggct gac att ctc ttc tgt gag tca gcc ctc ttt tat ttc tct gag 1322 Leu AlaAsp Ile Leu Phe Cys Glu Ser Ala Leu Phe Tyr Phe Ser Glu 380 385 390 395tac atg gaa aaa gag gat gca gtg aat atc tta caa ttc tgg ttg gca 1370 TyrMet Glu Lys Glu Asp Ala Val Asn Ile Leu Gln Phe Trp Leu Ala 400 405 410gca gat aac ttc cag tct cag ctt gct gcc aaa aag ggg caa tat gat 1418 AlaAsp Asn Phe Gln Ser Gln Leu Ala Ala Lys Lys Gly Gln Tyr Asp 415 420 425gga cag gag gca cag aat gat gcc atg att tta tat gac aag tac ttc 1466 GlyGln Glu Ala Gln Asn Asp Ala Met Ile Leu Tyr Asp Lys Tyr Phe 430 435 440tcc ctc caa gcc aca cat cct ctt gga ttt gat gat gtt gta cga tta 1514 SerLeu Gln Ala Thr His Pro Leu Gly Phe Asp Asp Val Val Arg Leu 445 450 455gaa att gaa tcc aat atc tgc agg gaa ggt ggg cca ctc ccc aac tgt 1562 GluIle Glu Ser Asn Ile Cys Arg Glu Gly Gly Pro Leu Pro Asn Cys 460 465 470475 ttc aca act cca tta cgt cag gcc tgg aca acc atg gag aag gtc ttt 1610Phe Thr Thr Pro Leu Arg Gln Ala Trp Thr Thr Met Glu Lys Val Phe 480 485490 ttg cct ggc ttt ctg tcc agc aat ctt tat tat aaa tat ttg aat gat 1658Leu Pro Gly Phe Leu Ser Ser Asn Leu Tyr Tyr Lys Tyr Leu Asn Asp 495 500505 ctc atc cat tcg gtt cga gga gat gaa ttt ctg ggc ggg aac gtg tcg 1706Leu Ile His Ser Val Arg Gly Asp Glu Phe Leu Gly Gly Asn Val Ser 510 515520 ccg act gct cct ggc tct gtt ggc cct cct gat gag tct cac cca ggg 1754Pro Thr Ala Pro Gly Ser Val Gly Pro Pro Asp Glu Ser His Pro Gly 525 530535 agt tct gac agc tct gcg tct cag tcc agt gtg aaa aaa gcc agt att 1802Ser Ser Asp Ser Ser Ala Ser Gln Ser Ser Val Lys Lys Ala Ser Ile 540 545550 555 aaa ata ctg aaa aat ttt gat gaa gcg ata att gtg gat gcg gca agt1850 Lys Ile Leu Lys Asn Phe Asp Glu Ala Ile Ile Val Asp Ala Ala Ser 560565 570 ctg gat cca gaa tct tta tat caa cgg aca tat gcc ggg aag atg aca1898 Leu Asp Pro Glu Ser Leu Tyr Gln Arg Thr Tyr Ala Gly Lys Met Thr 575580 585 ttt gga aga gtg agt gac ttg ggg caa ttc atc cgg gaa tct gag cct1946 Phe Gly Arg Val Ser Asp Leu Gly Gln Phe Ile Arg Glu Ser Glu Pro 590595 600 gaa cct gat gta agg aaa tca aaa gga tcc atg ttc tca caa gct atg1994 Glu Pro Asp Val Arg Lys Ser Lys Gly Ser Met Phe Ser Gln Ala Met 605610 615 aag aaa tgg gtg caa gga aat act gat gag gcc cag gaa gag cta gct2042 Lys Lys Trp Val Gln Gly Asn Thr Asp Glu Ala Gln Glu Glu Leu Ala 620625 630 635 tgg aag att gct aaa atg ata gtc agt gac gtt atg cag cag gctcag 2090 Trp Lys Ile Ala Lys Met Ile Val Ser Asp Val Met Gln Gln Ala Gln640 645 650 tat gat caa ccg tta gag aaa tct aca aag tta tga ctcaaaactt2136 Tyr Asp Gln Pro Leu Glu Lys Ser Thr Lys Leu * 655 660 gagataaaggaaatctgctt gtgaaaaata agagaacttt tttcccttgg ttggattctt 2196 caacacagccaatgaaaaca gcactatatt tctgatctgt cactgttgtt tccagggaga 2256 gaatggggagacaatcctag gacttccacc ctaatgcagt tacctgtagg gcataattgg 2316 atggcacatgatgtttcaca cagtgaggag tctttaaagg ttaccaa 2363 <210> SEQ ID NO 34 <211>LENGTH: 662 <212> TYPE: PRT <213> ORGANISM: Homo Sapien <400> SEQUENCE:34 Met Arg Gly Ala Gly Pro Ser Pro Arg Gln Ser Pro Arg Thr Leu Arg 1 510 15 Pro Asp Pro Gly Pro Ala Met Ser Phe Phe Arg Arg Lys Val Lys Gly 2025 30 Lys Glu Gln Glu Lys Thr Ser Asp Val Lys Ser Ile Lys Ala Ser Ile 3540 45 Ser Val His Ser Pro Gln Lys Ser Thr Lys Asn His Ala Leu Leu Glu 5055 60 Ala Ala Gly Pro Ser His Val Ala Ile Asn Ala Ile Ser Ala Asn Met 6570 75 80 Asp Ser Phe Ser Ser Ser Arg Thr Ala Thr Leu Lys Lys Gln Pro Ser85 90 95 His Met Glu Ala Ala His Phe Gly Asp Leu Gly Arg Ser Cys Leu Asp100 105 110 Tyr Gln Thr Gln Glu Thr Lys Ser Ser Leu Ser Lys Thr Leu GluGln 115 120 125 Val Leu His Asp Thr Ile Val Leu Pro Tyr Phe Ile Gln PheMet Glu 130 135 140 Leu Arg Arg Met Glu His Leu Val Lys Phe Trp Leu GluAla Glu Ser 145 150 155 160 Phe His Ser Thr Thr Trp Ser Arg Ile Arg AlaHis Ser Leu Asn Thr 165 170 175 Met Lys Gln Ser Ser Leu Ala Glu Pro ValSer Pro Ser Lys Lys His 180 185 190 Glu Thr Thr Ala Ser Phe Leu Thr AspSer Leu Asp Lys Arg Leu Glu 195 200 205 Asp Ser Gly Ser Ala Gln Leu PheMet Thr His Ser Glu Gly Ile Asp 210 215 220 Leu Asn Asn Arg Thr Asn SerThr Gln Asn His Leu Leu Leu Ser Gln 225 230 235 240 Glu Cys Asp Ser AlaHis Ser Leu Arg Leu Glu Met Ala Arg Ala Gly 245 250 255 Thr His Gln ValSer Met Glu Thr Gln Glu Ser Ser Ser Thr Leu Thr 260 265 270 Val Ala SerArg Asn Ser Pro Ala Ser Pro Leu Lys Glu Leu Ser Gly 275 280 285 Lys LeuMet Lys Ser Ile Glu Gln Asp Ala Val Asn Thr Phe Thr Lys 290 295 300 TyrIle Ser Pro Asp Ala Ala Lys Pro Ile Pro Ile Thr Glu Ala Met 305 310 315320 Arg Asn Asp Ile Ile Ala Arg Ile Cys Gly Glu Asp Gly Gln Val Asp 325330 335 Pro Asn Cys Phe Val Leu Ala Gln Ser Ile Val Phe Ser Ala Met Glu340 345 350 Gln Glu His Phe Ser Glu Phe Leu Arg Ser His His Phe Cys LysTyr 355 360 365 Gln Ile Glu Val Leu Thr Ser Gly Thr Val Tyr Leu Ala AspIle Leu 370 375 380 Phe Cys Glu Ser Ala Leu Phe Tyr Phe Ser Glu Tyr MetGlu Lys Glu 385 390 395 400 Asp Ala Val Asn Ile Leu Gln Phe Trp Leu AlaAla Asp Asn Phe Gln 405 410 415 Ser Gln Leu Ala Ala Lys Lys Gly Gln TyrAsp Gly Gln Glu Ala Gln 420 425 430 Asn Asp Ala Met Ile Leu Tyr Asp LysTyr Phe Ser Leu Gln Ala Thr 435 440 445 His Pro Leu Gly Phe Asp Asp ValVal Arg Leu Glu Ile Glu Ser Asn 450 455 460 Ile Cys Arg Glu Gly Gly ProLeu Pro Asn Cys Phe Thr Thr Pro Leu 465 470 475 480 Arg Gln Ala Trp ThrThr Met Glu Lys Val Phe Leu Pro Gly Phe Leu 485 490 495 Ser Ser Asn LeuTyr Tyr Lys Tyr Leu Asn Asp Leu Ile His Ser Val 500 505 510 Arg Gly AspGlu Phe Leu Gly Gly Asn Val Ser Pro Thr Ala Pro Gly 515 520 525 Ser ValGly Pro Pro Asp Glu Ser His Pro Gly Ser Ser Asp Ser Ser 530 535 540 AlaSer Gln Ser Ser Val Lys Lys Ala Ser Ile Lys Ile Leu Lys Asn 545 550 555560 Phe Asp Glu Ala Ile Ile Val Asp Ala Ala Ser Leu Asp Pro Glu Ser 565570 575 Leu Tyr Gln Arg Thr Tyr Ala Gly Lys Met Thr Phe Gly Arg Val Ser580 585 590 Asp Leu Gly Gln Phe Ile Arg Glu Ser Glu Pro Glu Pro Asp ValArg 595 600 605 Lys Ser Lys Gly Ser Met Phe Ser Gln Ala Met Lys Lys TrpVal Gln 610 615 620 Gly Asn Thr Asp Glu Ala Gln Glu Glu Leu Ala Trp LysIle Ala Lys 625 630 635 640 Met Ile Val Ser Asp Val Met Gln Gln Ala GlnTyr Asp Gln Pro Leu 645 650 655 Glu Lys Ser Thr Lys Leu 660 <210> SEQ IDNO 35 <211> LENGTH: 162025 <212> TYPE: DNA <213> ORGANISM: Homo Sapien<300> PUBLICATION INFORMATION: <308> DATABASE ACCESSION NUMBER: GenBankAC005730 <309> DATABASE ENTRY DATE: 1998-10-22 <400> SEQUENCE: 35gaattcctat ttcaaaagaa acaaatgggc caagtatggt ggctcatacc tgtaatccca 60gcactttggg aggccgaggt gagtgggtca cttgaggtca ggagttccag gccagtctgg 120ccaacatggt gaaacactgt ctctactaaa aatacaaaaa ttagccgggc gtggtggcgg 180gcacctgtaa tcccagctac tcaggaggct gaggcaggag aattgcttga acctgggaga 240tggaggttgc agtgagccga gatcgcgcca ctgctctcca gcctgggtgg cagagtgaga 300ctctgtctca aaaagaaaca aagaaataaa tgaaacaatt ttgttcacat atatttcaca 360aatttgaaat gttaaaggta ttatggtcac tgatatcctg tttcattctt tatataatca 420ttaagtttga aatgtatact tgcactacta acacagtagt taatcttagt cctacaagtt 480actgctttta cacaatatat tttcgtaata tgtatgcact ggtgtttatg tacgtgttta 540tgtttatatc tgttaaaatt agcagtttcc atctttttct attttgtacc atcacatcag 600ttcagaagga ttgacagagc aaaatgattt gatgaagtat aaaagtcaca tggtgagtgg 660cataaataca actctgaaca attaggaggc tcactattga ctggaactaa actgcaagcc 720agaaagacac atatcctata tgtcaagaga tgtaccaccc aggcagttaa agaagggaag 780tacacataga aagcacaatg gtgaataatt aaaaaattgg aatttatcag acactggatt 840catttgctcc taaagtcaga gtcctctatt gtttttttgt ttttgtgggt ttctttttaa 900atttttttat tttttgtaga gtcggagtct cactgtgtta cccgggctgg tctagaactc 960ctggcctcaa acaaacctcc tgcctcagct tcccaaagca ttgggattac agacatgagc 1020cactgagccc agcccagacg ctttagcatt tatgaagctt ctgaaatagt tgtagaaacc 1080gcataagctt tccatgtcac tttcaaagtt tgatggtctc tttagtaaac caaccaagtt 1140attcctcaag ggcaaaataa catttctcag tgcaaaactg atgcacttca ttaccaaaag 1200gaaaagacca caactataga ggcgtcattg aaagctgcac tcttcagagg ccaaaaaaaa 1260aggtacaaac acatactaat ggaacattct ttagaagagc cccaaagtta atgataaaca 1320ttttcatcaa agagaaaaga gaacaaggtg ttagcaaatt cctctatcaa ataacactaa 1380acatcaagga acatcaatgg catgccatgt ggaagaggaa gtgctagctc atgtacaaac 1440cagtagataa tttcaacttg ctgccgaatg aaacctcttt gcaaggtatg aatcagcact 1500tctcatgttt gttttgcttt gttttgtttt gtttttagag acaggccctt gctctgtcac 1560acaggctgga gtgcagtggc acgatcagag ctcactgcaa cctgaaactc ctgggctcaa 1620gggatcctcc tgccttagcc tcccaagtag ctgggactac aggcccacca tgcccagcta 1680attttttaaa ttttctatag agatgggatc tcactagcac ctttcatgtt tgatgttcat 1740atacaacgac caaggtacaa tgtggaaaag ggtctcaggg atctaaagtg aaggaggacc 1800agaaagaaaa ggggttgcta catagagtag aagaagttgc acttcatgcc agtctacaac 1860actgctgttt tcctcagagc agagttgatg atctaaatca ggggtcccca acccccagtt 1920catagcctgt taggaaccgg gccacacagc aggaggtgag caataggcaa gcgagcatta 1980ccacctgggc ttcacctccc gtcagatcag tgatgtcatt agattctcat aggaccatga 2040accctattgt gaactgagca tgcaagggat gtaggttttc cgctctttat gagactctaa 2100tgccggaaga tctgtcactg tcttccatca ccctgagatg ggaacatcta gttgcaggaa 2160aacaacctca gggctcccat tgattctata ttacagtgag ttgtatcatt atttcattct 2220atattacaat gtaataataa tagaaataaa ggcacaatag gccaggcgtg gtggctcaca 2280cctgtaatcc cagcacttcg ggaggccaag gcaggcggat cacgaggtca ggagatcgag 2340accatcctgg ctaaaacggt gaaaccccgt ctactaaaaa ttcaaaaaaa aattagccgg 2400gtgtggtggt gggcacctgt agtcccagct actcgagagg ctgaggcagg agaatggtgt 2460gaacctggga ggcagagctt gaggtaagcc gagatcacgc cactgcactc cagcctgggc 2520gacagagcga tactctgtct caaaaaaaaa aaaaaaaaaa aaagaaataa agtgaacaat 2580aaatgtaatg tggctgaatc attccaaaac aatcccccca ccccagttca cggaaaaatt 2640ctcccacaaa accagtccct ggtgccaaaa aggttgggga ccgctaatct aaataatcta 2700atcttcattc aatgctaaaa aatgaataaa ctttttttta aatacacggt ctcactttgt 2760tgcccaggct ggagtacggt ggcatgatca cagctcactg tagcctcaat cacccaggcc 2820ccagcgatcc tcccacctaa acttcctgag tagctgggac tacaggcacg caccaccatg 2880cccagctaat ttttaaattt tttatagaga tgggggtctc accatgttgc ccagactggt 2940ctcaaaccct gggctcaagt gatcctccct caaactcctg gactcaagtg atcctccttc 3000cttggcctcc caaagtgctg ggattacaag catgagccac tgtacccagc tggataaaca 3060ttttaagtcg cactacagtc atggacaatc aggcttttca acatgcagta tggacagtga 3120gtcccagggt ctgcttttcc atactgaaat acatgtgata ctaaggagaa aggtgctcgc 3180aaggatattt aaaatgaaga atatttaaaa tgaggaaaaa actgtttctt catgactttg 3240ataaggctga taaagaccat ttctgtgatc tcaggtgatt cactcaagta gtatatttca 3300gtaatcatta tctggaacag cctgaatctt aaccaaaata ccatgatttt ttaatgctgt 3360tatgatacct tgatgatatg accaaactgc aatgtaggca gctaaatctc cacgagtttg 3420acttccccga gagttgacag ttttcttcac aaattaaaga aatatatttt ttgatacatg 3480attggcatat ttaaaaacta cactgaaatg ctgcaaaatg atataaagaa acattttcca 3540gaatcaaatg caatcaaaga gtggattagg aatctactca ccattatcaa ctaaatagaa 3600acacttggac tgggtgtggt ggctcacatc tgtaatctca gcactttggg aggccaaggc 3660aggtggattg cttgaggcca ggagctcaag accagcctga gcaacatagc aaaactctgt 3720ctctacaaaa aaaaaaaaaa attaaccagg catggtggca gatgcttgta atcccagcta 3780ctctggaagc tgaagtagga ggactgcttg agcccaggag atcaagactg cagtgagccg 3840tggtcatgct gcgccacagc ctgagtgaca gagagagacc ctgtctcaaa aacaaaaaca 3900aacaaaaaac acttaacctt cctgtttttt gctgttgttg ttgttgtttg tttgttttga 3960gatggagtct cactctgttg cccaggctgg agtgcagtgg cgtgatcttg gctcactgca 4020agctctgcct cccgggttca cgccattctc ctgcctcagc ctcccgagta gctgggacta 4080taggcgcccg ccaccacgcc cggctacttt tttgcatttt tagtagagat ggggtttcac 4140cgtgttagcc aggatggtct tgatctcctg acctcgtgat ccacctgcct cggcctccca 4200aagtgctggg attacaggca tgagccaccg cacccggcca acctttctgt tttttagttt 4260gatatgcttg ttaactcagc agctgaaaga atgctgaaag tggccttcag taaaaaaatt 4320tcactagaat ctctacatcc atatttaatc tgaatgcata tccagattga tcagttagag 4380caaaaacact catcatcatt cctgatgacc tctaattctg gtttcggctt tctatttcaa 4440tggaaacaga ataaggaaag aaatggaagg gctctggaaa tttgtcctgg gctatagata 4500ctatcaaaga tcaccaacaa taagatctct cctataaata taaaacaagt ataattaatt 4560ttttaattat ttttttctct tcagaggatt ttatttcaag ataaaacata acttctaccc 4620atactattga ttccaaaggt tagaaaaagt gtttttcctc atcttatcct tcaaagaggt 4680cacagcaatg caaacatcta taaaatgcct ctgcataatt gtcagaagct atagtccaga 4740aatcattgaa aatgcttttc cattttaagc ttaggtgagg tgtcttagga aacctctatg 4800acaacttact ctatttattg ggaggtaaac tcccagactc tcccagggtc tcctgtattg 4860atctcatttt ttaggcttcc taatcccttg aagcacaatc gaaaaagccc tggatctctt 4920ttctgcacat atcatcgcgg aattcattcg gcttccagca agctgacact ccatgataca 4980agcggcctcg cccttctccg gacgccagtc cttgctgcgg ttagctagga tgaggggttt 5040gctgggcttc agtgcaggct tctgcgggtt cccaagccgc accaggtggc ctcacaggct 5100ggatgtcacc attgcacact gagctcctgg caggctgtac caatttttta attatttaat 5160atttattttt aaaattatgg tgaatatttt ggtattctgc tctaaaatag gcccataaat 5220gcacagcaga tatctcttgg aacccacagc tttccactgg aagaactaag tatttttctt 5280ttaaagatgc tactaagtct ctgaaaagtc cagatcctct acctctttcc atcccaaact 5340aagacttgga atttatgaga gatctagcta acagaaatcc cagacacatc attggttctt 5400cccagagtgc agtcctccta aagaggctca gccctaagca ggcccctgca ccaggagggt 5460gggtctgaga cccacatagc acttcccaag gtgcatgctc cagagaggca ctgaaacagc 5520tgagcacaag cctgcaagcc tggagaactc tcacagtcag aacggagggg gcccagtggg 5580actaacataa agagaaaagg gaacacagag aaatggatgg caccaacaac cagcaaagcc 5640ttcatggcca atgaaagcat cagtgacggg gccagaaccc tcatccccaa agactcttca 5700ctgcctttag tgaaaaacaa tggctagaga gtgaagttat gatcatgtat agagaggtaa 5760agttacattt ttatattctg actctgctaa tgtgaaattc cctatctgct agactaaaag 5820tttcagacac cctgttcaaa tatcccatta gttgctagag acttaaaatg aacagaacgc 5880acattgtcag gatgactatt accaaaaaat caaaagacag caagtattgg tgaggatgta 5940gagaaactgg aacttttgtg cactgtttat gagaatgtaa aatggagcag ctgctgtgga 6000aaagagtatg caggttcctc aaagagtaaa accaagatgt ggaaacaact aaatgcccat 6060cagtggatga aggggtagac aatatgtggt atatacatac catggagtac tattcagcct 6120ctaaaaaaaa aaaaggaaat tctataacat gcaacagcat ggatgaatct tgaggacatt 6180ttgctaatga aataaggcag tcatagaaag acaaatactg cacgactcca cttatatgag 6240ataccaaaaa tagacaaatt catagaatca aagagtacaa tggaggttac ctggagctgc 6300agggcgggaa acgaggagtt actaatcaac gaacataacg ttgcagttaa gtaagatgaa 6360taagctctca agatcagctg tacaacactg tacctagagt caacaataat gtattgtaca 6420cttaaaaatt tgttaagggt agattaacaa atgtagtaga tccacaaatg tggttaagtg 6480ttcttaccac agtaaaataa aaaaagaata tcaagcccag gagttcgaga ctagcctggg 6540taacatggtg aaaccctgtc tctacagaaa atacaaaaat tagccagctg tggaggtgca 6600ctcctaggga ggctgaggtg ggaggcttgc ttgagcccag gaggtcaagg ctgcagtgag 6660ccatgattgc accactgtac tccagcccag atgacagagc aagacaccac cccccccaaa 6720aaaagaaaaa gaatatcaaa cattttaaaa gatcagatac gcaagaacaa caacaaaaaa 6780gagatgaaca gagcatcgac cctcatctag tgggattctt ggtctaactg aaaaacagac 6840attgagagac aaacaatgac agtgatgtga tcacagcaat tacacaggta tcccctgggg 6900actgcagaag aaaggaggaa tgcctaactt tcagaaaata gagaaagcgt caaacagttg 6960gtgaaagcct tccaaaacta gagagaactg cacacaccaa atcacagaaa gaagaaaagc 7020cgtgggagat tctgggaccc accggctatt tttgatggct gaacaccctg ctgcaggaga 7080gacaggagct ggaaagcatg gtgggatgaa acctcaaaca gctttgcctg cattgcttaa 7140gatgactggg cttgattaac tctagtcaat ggggacaatt caatcaaaga agaaagatgc 7200tcaaattcac attttagaat gattttttat ggcagtatgg ggaatagatt aaaagagagt 7260gaagctggag gcaagaaact tgttaagagg caactgaaac agtctagatg ataaataata 7320aactgacaga gtgactagaa aaatcagaac aggctgaatc aacagatacc tagatgaaaa 7380taacaggact tgatcaccag ttgtatcttg gagaggaagg agttgtttcc ttgctttccc 7440tacgactggg aatacggaag gtttgccgtg tgtattggtt atatactggt gtgtagccaa 7500tcactgacaa ccatttagca gcttaaaaca caaaggctta tctcccagtt tctgtgggcc 7560aggaatctaa gataggctta gctggctggt tctggctcag agtttctcaa gaggttgcaa 7620tcaagatgtc agctggggtt gcatcatctg aaggctcaac tggggccgga gggtccactt 7680ccaaggagtt cactcacctg cctgacaagg cagtgctggt tgttggcagg agatctcaat 7740tcattgccaa gtgagcctct ctatagcatt gctggaacat cctccccatc tggcagttgg 7800cttctctcag catgagtgat ctgagagaga gagcaaggag gaagccacag tgttcttcct 7860actcctactc ctaacactat ggacctactc ctaacactct cacttctgcc ttattccatt 7920agttagaaag ggaactaagc tccacctctt gaaataagaa gtgtcaaaga atttgtggat 7980atatttaaaa atcatcacac tgtggaagtg gatagggggt tcaattaatg ctgaacttga 8040aatgcctgag acattcaaat gtccaacagg caatgaacat acccatagat ggtcatgact 8100ttagcaagaa tagaggaaga tcacagaatt aaggaggaat tgaaaggtaa aagaagtgga 8160gtcagattcc ccctgaaaag tgagccatga aaggaacttt aactattgag ttagaggtca 8220gagtaggaaa tttcggtgga attctttttt aaagaaagga accatataag catgttttga 8280ggtagaggga gaataaatca gtagacaggg agaggtaaaa aacataaatg ataggggata 8340gttgacaaag gtcttggcag aatcccttac ccattgactt ggggccaaga gagggacact 8400tctttgtttg agggataagg aaaataagaa agaatgggtg ctatttagtg tggtcctgtc 8460tctagggcaa acgcataggt aacaaactgt gtgtgttagg aatatagatg tgacctcaca 8520ttgagattct cacctcaaat ccattttgtt gttacctgta ccttcctacc ttctcttttt 8580gctacatgca gactgctgtt ttgtcttcct ggcctgttcc aggtttcagc attctggcat 8640atctgctacc ctgttcccaa acctctctag agtccatgct ccttccttgg atagtgtttg 8700attgggccac gtatctaaga agtgatgcct tcagttaggc ctgagaacct cctctatgga 8760aatctccatc agtgaccctg acagacttgg tatcttggag atgtcactgc tcccagcctg 8820tggtctagga gaatctcagc ctgggcctct agtagtatgg ataaggcgtt aaggtatctt 8880tgaaccagag tctgtcatat tcctcaatgt gggacagata aaacagtggt agtgctggtg 8940tttctgagct agaactctgg tttttggtct agattctttg atgtatgacc tttcagaggt 9000attaaaattt gttctaatac aatgttcaat acaaatgtag ttccttttct gttaggacct 9060caacaaaaca tgaccaactg tagatgaaca ttaaactatg acaattcatg gaaatgaata 9120cagtaatacc tgcggttccc ccattttagc agtcactatg gtgacatttg gcacaaatgg 9180ctatttaagg gtgcttttgt taaaacctac catcttacta ggcacatgat attgaaacta 9240atgaaataat ggagaaactt cttaaaaact tttaatgaat aaagtgatga agtgataata 9300ttttagctgc tatttataaa gtgactatta caggtcaaac attcttctag ggtttttttg 9360ttgaagttgt cacatttaat ccttaataac ccactatgag tcaggtattc ttctctcccc 9420tttggacagt tggggaaatg ggggtcagag aggttaggta atttgctcag ggccacacaa 9480cctgcatgta gaaaatctga gatttgtaca ggaacgtatc aaactctgaa gtccatgctt 9540ctattttccc atgctgcctt tctaataaaa ggtaactaat gctactggat gctgccccca 9600aagtgagtca ctttcacccc accctacttg attttctcca taaaactaat cacatcctga 9660caacttattt attgctgatc tcccccacta gattataaac tcaataaaag caagatcctt 9720gtctgctgaa tatcagtacc taaaacgctg tctagcacag agcaagtaat taatatttgt 9780tgaatgaaca aataaaggaa aaaaattcaa aggaagaaaa agccctaaaa cagatgttta 9840cctaaacata cattttaaaa gaaagcatat aacaaattca ggacagaatt taaatttgat 9900tttttaaaga aataaccaag tgctagctgg gcacagtggc tcacacctgt aatcctagca 9960ctctgggagg ccgaggcagg cagatcactt gaggtcaaga gttcaagacc agcctggcca 10020acatggtgaa acctgtctct actaaaaata cagaaattat ccaggcatgg tggcaggtcc 10080ctgtaacccc agctactcag gaggctgagt caggagaatt gcttgaaccc aggaggcaga 10140ggttgcagtg ggccaagatt gcaccactgc actccagcct gagtaacaaa gcaagactct 10200gtctgaagga gaaggaaaga aagaaggaaa gaaggaaaga aggaaagaag gaaagaagga 10260aagaaagaaa gaaagaaaga aagaaagaaa gaaagaaaga aagaaagaaa gaaagaaaga 10320aagaaagaaa aagaaagaaa gaaagaaaga accaagtgct tatttgggac ctactatgct 10380atgtttttcc atgcacgcta ttttcagtaa agcagttagc aaacttgcaa gatcataaca 10440acaaatatat gcttctataa ctctaaaatt gtgctttaag aagttcctct ttaccagctc 10500atgtatgcat tagttttcta agagttacta gtaacttttt ccctggagaa tatccacagc 10560cagtttattt aaccaaagga ggatgcttac taacatgaag ttatcaaatg tgagcctaag 10620ttgggccagt tcatgttaat atactccaga acaaaaacca tcctactgtc ctctgacaat 10680tttacctgaa aattcatttt ccacattacc aaggagccag ggtaggagaa tatagaaaga 10740ccacccaaga atccttactt ctttcagcaa aatcaattca aagtaggtaa ctaaacacat 10800gccctaacaa tgaatagcag attgtgctca gaagaatgat ctacaacatc ttactgtgaa 10860ggaactactg aaatattcca ataagacttc tctccaaaat gattttattg aatttgcatt 10920ttaaaaaata ttttaagcct aaattttaaa aggtttgata ttggtacatg aatagacaaa 10980cagacatgga ctagaccaag aattaggttc aaacatatac aggaatttaa tatacgataa 11040atctagtatt ccaaaggaac caacaaatgg tgttcagaca gcaggatagg catcaggaaa 11100aacacagttg ggcaccctac cttactccta acaccaggag taactgaagg agcaccaaat 11160atttatttat tttaattata gttttaagtt ctagggtacg tgtgcacaac atgcaggttt 11220attacatagg tatacatgtg ccatgttggt gaggagcacc aaatatttaa aagaaaaaaa 11280ttggccaggg gcggtggctc acacctgtaa tcccagcact ttgggaggcc aaggtgggca 11340gatcacctga ggtcgggagt tcgagaccag cctgagcaac atggagaaac cccatctcta 11400ctaaaaatac aaaattagcc aggcatggtg gcacatgcct gtaatcccag ctacttggga 11460ggctgaggca ggagaatagc tttaatctgg gaggcacagg ttgcggtgag ctgagatatt 11520gcactccagc ctgggcaaca agagcaaaac ttcaactcaa aaaaattaat aaataaataa 11580aaataaagaa agaaaagaaa aaaatgaaaa tagtataatt agcagaagaa aacaccgtag 11640aatcctcgga ctcttaggat ggggaatgcc tataatataa aaaccctgaa gttataaaag 11700agaaaatcac ctacatacaa accaaatctt tctacatgcc taaaacatag cacaaacaca 11760gctaaataat catagctgaa tgaactggga aaacaaaact tgactcatat ccagacagag 11820ttaattttcc tacacataaa gagtacctat ataaacccaa caaaaaaacc accactaacc 11880caaaataaaa atgtgacagg taatgaacag gtagttcaca gagaatacaa atggctcttc 11940ggcacataag atgctcagac tgacttttac ttatttattt tttgagagac agggtctcac 12000gatgttgccc aggttaggct caaactcctg ggctcaaatg atagtaccag gactacaggt 12060gtgccccacc gcacctggct cctcaaccac ctgtattaac aggaaatgca aaataaaact 12120ttcaaatcta ttttacctat tagaatggca aaaatttgaa aaacttcaaa catcatcatg 12180ttggtgagaa tgtgaggaga ctggcactct cattttttgc tgatagcata tatatactga 12240tggcttctat ggaaagcaat ctggcagcgt ctatcaaatg tacaagtgca tatatccttt 12300gacaaagcaa ttccactcta ggaatgtgtt ctatatggtt gtgcttcctg gggctgggaa 12360ctgggagcta agggacaggg gcagaagata atcttctttt ccctccttcc ccgttaaaca 12420tgttgaattt tatatactgt aatatattat ttttcacaaa agataatttt taagcgatat 12480gtctgggaat tttttttttt cttttctgag acagggtctc actctgtcat ccaggctgga 12540atgccatggt atgatctcag ctgactgcag cctcgacctc ctgggttcaa gcaatcctcc 12600cacctcagcc tcctgagtag ctgggactac aggcacgtgc catcatgcta atttttgtat 12660atacagggtc tcactatgtt gcccaggcta atgtcaaact cctaggctca agcaatccac 12720ccacctcagg ctccaaagtg ctgggattac aggcgtgagc caccgcgcct ggccctggga 12780attcttacaa aagaaaaaat atctactctc cccttctatt aaagtcaaaa cagagaagga 12840aattcaacct ataatgaaag tagagaaggg cctcaaccct gagcaacaaa cacaaaggct 12900atttctgaga caggaatttg ctgaacaaaa tcgagggaag atgacaagaa tcaagactca 12960cttctcggct gggcgcagtg gctcacacct gtaatcccag cactttggga ggccgaggcg 13020gacagatcac gaggtcagga gattgagacc atactggcta acacagtgaa acccagtctc 13080tactaaaaat acaaaaaatt agccgggcgt ggtggcaggt gcctgtagtc ccagctactt 13140gggaagctga ggcaggagaa tggcgtgaac ccaggaagcg gagcttgcag tgagccgaga 13200tcacgccact gcactccagc ctgggtgaca gagcaagact ctgtctcaaa aaaaaaaaaa 13260aagactcatt tctctagatc ttgagccgta ttcaaattta tctcagctta gtgagaggtt 13320aaagcaagga atatccttcc ctgtgggccc tgctccttac tgaaggaagg taacggatga 13380gtcaaggaca ccaatggaga aaagcactaa caccattatc tgatgaacat tacgtgaaga 13440agggtaagaa gtgaagtgga attgctgaag aagtcagtga aagcggacat tcatttgggg 13500aaatggaata taggaaatcc ataaaagtga ttaaaaagat gttagaggct gaggcggggg 13560gaccacaggg tcaggagatc gagaccatcc tggctaacac ggtgaaaccc catctctact 13620aaaaatacaa aaaattagcc aggcgtggtg gcaggcacct gtagtcccaa ctactcggga 13680gactgaggca ggagaatggc atgaacctgg gagacggagc ttgcagtgag ccgagatcac 13740gccactgcac tccagcctgg gtgacagagt gagactccat ctcaaaaaaa aaagttagat 13800acgagagata aagatccaac agacacacaa ctgctaattc tgaacagaac aaaacaaatg 13860gcacaggaaa agaaaattta agatataaca ccggaaaact ttcctgaaat tgagtaactg 13920aatctatagc ttgaaagggt ttagcatatg ccaagaaaaa tcagtagagt ccaaccagca 13980caagacacat ctagcaaggc tggtgattct accaacacag agaaagaagt gggtgaccca 14040taatgcggaa aaaggcagac catctgcagt cttctccaga acactggagt ctgaagacaa 14100aagaatgctg cctactgagc cagaagggag agaaagtgac ccaacacatc tttaccaagt 14160tagaatgtca cgcattattt aaaggctgca aaagccatga aagacatgaa agaacacaag 14220catttacaac atgaaagaac acaagcattc tcatactcaa gaatccttaa gaaaaatgta 14280gtcctaatcc agcccactga aagttaaatg tacttaatgt gctcattaat gggaacttca 14340tagcttcaaa tcagtctggt cccatctacc aacatctctc gcccggcttt cctgcaatag 14400tcagcacctt tccctcctcc cagtcttgtc ccctggagtc tgctctcagc atagcagagt 14460gaccacatca acacccaagt cagagccctc cagtgcgcac tggtctacaa agcccttccc 14520accccccacc ccacgtgccc tccggatcct tgtgacgtgt ctcctgcata ccctagcagc 14580cctggcctcc tcactgcccc tcctgtacat caggaaggcg actccttgag tcttggctct 14640ggccgcctcc tccacctgca gtgagttaac tcccttacct actctaggtc attgctcaaa 14700tgtcagcatc tcaatggggc cctccctgac taccctattt aaattctaca tactcccctt 14760gaccccatgg acctcactca ccctattcca cttttattct tacaatttag cacttgttct 14820cttctaacgt attctaagac ttactcattt attacattgt ttgccacccc ctctagtaca 14880taaactccag aggggcaggg atttctgtct atttattcat ttctttatcc ctaggacata 14940gaacagggca tagttcagag tattcaatgt tatcaatgaa tgaactagca gtagtaccag 15000ttccagttag gcacagaatt aaatctaaat agaattaaat ctcatggtct gggttaacta 15060tggatagaaa attagatata attttaagaa gcctagaaag aaaaaattaa taatgtaaaa 15120ataatattaa tttgataata ataacaaaaa ctctgccagg cactgtggct caaatctgca 15180atcccagcta ctcaggaggc tgaggtggaa ggatcacttg agaccagagt tcaagactca 15240gcctaggcaa cacggcaaga aactgtctct aaaaaaatta aaacttaaat ttttaaaaaa 15300gaattctcaa agcgtcacaa aaactggaga ttaaggtaca ggaagtgtga agtaatatta 15360ctatgctaat ggtttttttt ttttttagaa aggtataacc aaaagatttc tttctcaagt 15420cgataaactg agaaagataa gcatatcttc caattaacag agggggagga aaagccagat 15480acaacaaaat aagatataaa ttagtttcca gttgaaaaca agagtaggag ttattttgca 15540tcacctcacc tgtgacctcc cccagcccaa aaaacactac tgataaacag ggtagaaaag 15600catcatctca gataaagcag gaaaaactgc cacagtctca aaccacaaac tataagcaca 15660cacctggcca accctgccaa gtctgggctc agtaggagga acgtgctgag agctaggatg 15720taccaactta gacattctgt gggatacaga tgtccctgga agggtcacac catctcaaag 15780gcacctgtaa tgcccactga ttacagccac catatgtgag agagaaactc agggcactta 15840gagagtataa caagaacctt atgtcatctg agatgaggaa tcctcagccc tgcaaattaa 15900ccaactcttt agaacaactg gcaaaacata aatatccaca acttttgttt cagtaattcc 15960actcttagat atcaatccaa agtacatgag acagcagata cacacacaaa atggtattta 16020ctgcagcatt gtttataata gcaaaaaaca agaaataatc catatgtctc aataggatac 16080tgggtacatg agggtatgta cccatcattc aaccatcaaa aagagtgata tggatgtcca 16140cagatggaca taaaaagctg tgtgttacgt gaaaacaaac tcaagcagca gcaggatggg 16200cttatgatag tcagtatgag ctaatttctg gaaaaaaaaa tctagtgtgt gcacagaaaa 16260catctgaaag aacagaaaca aaactatcag cagaatattg agatgtttta ctaagttgta 16320tatctatact gcttgtaatt tttaccccaa gcaagaatta ctttttggaa aaagaaaatt 16380caggaaataa agcatttctt taaacttcat gtttaaacaa atggtgatgg aataaaagag 16440ttcttattca tcataaacac acacagcaca catgcacgca tgtgcgtgag cacacccttt 16500acttgataaa taccatgttg aatattttag tctttccttt taggttctat cccttcactc 16560aaaatgcggt tataaataaa tgtacttttc atgtgccttc tgcctaaacc cactttaata 16620taactttaca gtcccattat cattatagtc tcaaagctag actcagcctg aaactaccct 16680ttcatttgga acccttatta aaatgccaca tacagctcct tcaaataaaa acaaacccta 16740ggacctgaca ctaggcttcc tttgttgcta ctcataatgg ccaagttctg tgcttataat 16800acatcttctt tcattttatt gctacatatc caagggtttt atatgttttt cttattatat 16860cttaattcaa aacaccatca cgctcttttc cagatgaaaa taaggaaaag aaattgagca 16920actgactgac ttaaaggtca taaaactata tagtagcaga gtcagcaaaa gaagaaacac 16980acatctccca agtagaggct gaaaaccagt accattcacc tccagggtga gctatataca 17040gattacaaag tcaccttctc taaatgttca aactgaatcc catacccata ctttaccact 17100acctcgtaag aacagcctca gatcttgtta tagccttttt tttagcatgc tgaagccaat 17160aaaatgcttc ccattcagca agagaaacaa gttctgaaac actgaataat ctgcccaggg 17220cctatgaaca tttccactgt gagaaatgtt ctccactgtg tggagaagat ccttactctt 17280ctccacacag gcagaacatt agaaaaattc ttggattcta tgatgcacag cttaggagtc 17340tgtttagcac aatttaagtc caaatagtta ttaaatcctc ctctgttcca gaaacagtgc 17400taaatactgt gaatataaaa attgaaaaga tactctcctg gctcccaaga aagtcagcca 17460gatagaggag acacaggcac acaaatcact gtcacatgaa gctctacctc cctaacttca 17520aacgagggcc taagtcacca agaatacagt agcagttgtg actacgagta actactataa 17580ttcaatactt tatcttccct tagaaaactc ttctcccttg gaaatttatt tgcatttcta 17640aataccattc cttactaaaa ggaagcaggg ctccttgggg aaatagctga ttctaggtgt 17700ggactatgaa atgaaaatgg tgagtctggg acatcccatg ttgcccagaa atcaaggaac 17760tgcccaaaga ttaacagagt catgttaaat ggacctaaga gtgaaccaga aggagctcac 17820tttgccccgc gtggaacaat ttcaagaaaa acatgacagt aatgaattat aaaacatgaa 17880ttaaaataca tattggtact aaaaagagaa caaaaggatg tggctttgga taaagctctt 17940cttcatggaa gaataccagc taataaatgt aaaggaaatg agagaattag aaaaattatc 18000attttgtaaa ccttaatata ttcacctaga catgctaaaa ccactgagta aaaggctgct 18060tgggaagagg atgctcacat gatctcagag tttcacacca cagataattt attagataca 18120ggaaggaaga tgtgatcaag cttcctgtga cccccagcca ggccccacaa cactatgtgc 18180ctccttgtga tgtgggagct acacagcatc gcccacacag cttctcgcca aaactgtttg 18240aagctaatca caagggaaga actggacagc ttctgaccat gagacgctcc accagacaac 18300ttgcttggcc tctccaaaga aacttgcttg gcctctccaa agaaaactca gtttcattta 18360aaaacaaaac taattattta aaaacaaacg aaaagcaagt tgtggacttg agctccaggg 18420acagagcaga catacttttc cctgttcttc ccagtaagtg gtaataaaaa ccctcaacac 18480tagatataaa acaaatataa gaaggttctg gaaggggaag aggaggcaga ctatccaggt 18540gccttgaggc ccacagaaca acccagtgat gggttcactg ggtcttcttt ttgcttcatt 18600atctcagact tggagctgaa gcagcaggca acttcaaaac accaaggggc acagattgaa 18660aagccccaag aaaagcctgc cctctctagc caaaggacca ggaaggagac agtctaatga 18720gatggaacac atttagacag taactgccca tttaccagca ataactgagc agggagccta 18780gacttccagt cttgtgagga cgtaccaagg tacccaacac ccccaccaag gctgagtaag 18840gactgcgact tttatccctg catggcagta gtaaggagcc catccctcac ccgccagcag 18900tgtcagggga acctggactt ccactcccac ccaggagtga tgaggccctc cctgctgggg 18960tcatgtcaga ggaggcctag tggagattca gtgacttaac cttttcccag agataatgag 19020gccacctttc ctccctcttc ccccatggtg acagtgaaag cactgtggca agcagtaggc 19080actcctaccc ctcctagcca gggaggtatc agggaggcca agtagggaac cagaataccc 19140acaaccaccc agcagcaaca ggggtccccc accccattgg gtgtcaatgg aagcagagcg 19200gaaagcctgg atatttaccc ccatctagaa gtaacaagct gatgtccccc ttcttctact 19260acaatggtgt tcaaaacagg tttaaataag gtctagagtc tgataacgta atacccaaat 19320cgttgaagtt ttcattgagg atcatttata ccaagagtca ggaagatccc aaactgaaag 19380agagaaaaga caattgacag acactagcac taagagagca cagatattag aactacctga 19440aaggatgtta aagcacatat cataagcctc aacaggctgg gcgcggtggc tcacgcctgt 19500aaccccagca ctttgggagg ccgaggcagg tggatcacaa gatcaggaga tcgagaccat 19560cctggctaac acggtgaaac cccgtctcta ctaaaaatac aaaaaaaaat agcaaggcat 19620ggtggtgggc acctgtagtc ccagctactc gggagcctga ggcaggagaa tggcatgaac 19680ctgggaagag gagcagtgag ccgagatcgc accaccgcac tccagcctgg gcaacagagc 19740aagacttcgt cccaaaaaaa aaaaaaaaaa aaaaaaaagc ctcaacaaac aactacaaac 19800gtgcttgaaa caaatgaaaa aaaaatcttg gcaaagaaat aaaagatata tattttggcc 19860aggtgcagtg gctcacagcc tgtaatccct gcactttggg aggctgaggc aggcggatca 19920cctgaggtca ggagtttgag accagcctga ccaacatgga gaaaccccgt ctctactaaa 19980aatacaaaat tagccagtca tggtggcaca tgcctgtaat cctagctact caggaggccg 20040aggcaggaga atcgcttgaa ctcaggaggt ggaggttgcg gtgagccgag atcccgccat 20100tgcacattgc actccagcct gggcaacaag agcaaaactc catctcaaaa aaatagatac 20160atattttaat ggaaatttta gaattgaaaa atacagtaac caaattgaat ggaaagacaa 20220catagaatgg agggggcaga caaaataatc agtgaacttc aacagaaaat aatagaaatt 20280acccaatatg aagaacagaa agaaaataga ctggccaaaa aataaagaag aaaaaagagg 20340agcagcagga ggaatgatgg aaaaagagaa aggaaggaag gaagggaagg agggagggaa 20400ggagtgaggg agaaagtctc aaagacctct gagactaaaa taaaagatct aacacttgtc 20460atcagggtcc aggaaagaga caaagatggc acagctggaa acgtattcaa aaaataatag 20520ctgaaaactt cccaaatttg gcaagagaca taaacctata gattcgaaat gctgaacccc 20580aaataaaaag cccaataaaa tccacaccaa aatacatcat agtcaaactt ctgaaaagac 20640gaaaagagaa aacgtcttga aagcagtgag tgaaacaaca cttcatgtat aagggaaaaa 20700caattcaagt aacagatttc ttacagaaat taaggaagcc agaaggaaat gacacaatgg 20760ttttcaagtg ctgaaagaaa agaagtgtca acacaaaatt ctagattcag taaaaatatc 20820cttcaagaat caatgggaaa tcaagacagt ctcagataaa gcaaaataag agaatatgtt 20880gccagcagat ctcccctaaa ggaatggcaa aaggaagatc atgcaacaga ccaaaaaatg 20940atgaaagaag gaatccagaa acatcaagaa gaaagaaata acatagtaag caaaaataca 21000tgtaattaca ataaaatttc tatctcctct taagacttct aaattatatt gatggttgaa 21060gcaaaaatta taaccctgtc tgaagtgctt ctactaaatg tatgcagaga attataaatg 21120gggaaagtat aggtttctat acctcattga agtggtaaaa tgacaacact gtgaaaagtt 21180acatacacac acacacgtaa gtatatataa atatatgtgt gtatatgtgt gtgtatatat 21240atatatacat ataatgtaat acagcaacca ctaacaacac tatacaaaga gataataacc 21300aaaaacaatt tagataaatt gaaatggaat tctaaaaaat attcaaatac tctacaggaa 21360gacaagacaa aaagagaaaa aaagaggagg acaaactaaa ttttttaaaa acataaataa 21420aatggtagac ttaagcccta acttatcaat aattacataa atgtaaatga tctaattata 21480tcaattaaaa gacagagata gcagagttaa tttaaaaaca tagctataag aaacctgctt 21540tgggctgagt gcagtgactc acacttgtaa tcccagcact tcgggaggcc aaggcgggtg 21600gatcacctga ggtcaggagt tccagaccag cctggacaac atggtaatac cccatctcta 21660ctaaaaatac aaaaaaatta gccaggcatg gtggcacacg cctgtagtcc caactactca 21720ggaggctgcg acacaagaac tgcttgaacc cgggcagcag aggtagcagt gggccaagat 21780tgcgccactc cagcctgaac gacagagtga gactccacct cagttgaaaa acaaaaaaga 21840aacctgcttt aaatatacca acatatgttg gttgaaatta aaagaataaa atatatcatg 21900aaaacattaa tcaaaagaaa ggagtggcta tattaataac ataaaataga cttcagagaa 21960aagaaaattt caagagacag gaataaaagg atcaagaaaa gatcctgaaa gaaaagcagg 22020caaatcaatc attctgcttg gagattcaac accctctctt aacaactgat agaacaacta 22080gacaaaaaaa tcagcatgga gttgagaaga acttaacacc actgaacaac aggatctaat 22140agacatttac ggaacactct acccaacaat agcaaaataa acattctttt caagtattca 22200ctgaacatat ccttagaccc taccctgggc cataaaacaa agctcactag tgattgccga 22260aggcttggat ggacagtgga agagctgcat ggggagggag aaggtgacag ttaaagagtg 22320taggatttct ttttgggata atgaaaatgt tccaaaattg attgtggtga tgttggcgca 22380actctacaaa tataaaaaag gccattgaat tgtacgtttt aagtgggtga aacatatggt 22440atgtggatta tatctaacgc tttttaaaaa cttaacacat ttcaaagaat agaagtcata 22500cagagtgtgc tctactggaa tcaaactaga aagaggtaac tggaggataa cgagaaaagc 22560ctccaaatac ttgaaaactg gacagcacat ttctaaaatc atccgtgggt caaagatatt 22620catttctgat attcattttt attgtttaat gtatttttaa aaatttctta agggaaataa 22680actgactaaa aatgaatatg gctgggtgcg gtggctcacg cctgtgatcc cagcactttg 22740ggaggccgag gctggtggat cacaagatca ggagttcgag accagcctgg ccaagatggt 22800gaaaccccgt ctcaactaaa aaactacaaa aagtagccaa gcgcagtggc gggagcctgt 22860ggtcccagct acttgggagg ctgaggtagg agaatcgctt gaacacaggc agcagaggtt 22920gcagtgagcc aagattgtgc cactgcacgc cagcctgggc gacagagact gcctcaaaaa 22980aaaaaaaaaa aaaaagaata tcaaaatttg tgggacatag ttaaagcaat gctgagaggg 23040aaatttataa cactaaatgt ttacattaga aaagagaaaa agtttcaaat caatagtctc 23100cactcccatc tcaagaacac agaagatgaa gagcaaaata aacccaaagc aagcaaaaga 23160aagaaaatat aaaaataaat cagtaaaatt gaaaacagaa acacaataaa gaaaatcagt 23220gaaacaaagt actgattctt cgaaagatta ataaaattga caaacctcta gcaaggctaa 23280caaacaaaaa agaaagaaga cacggattac cagttattag aatgaaagca taattagaaa 23340caactctaca cattataaat ttgacaatgt agatgaaatg gactaattac tgaaaaaaca 23400caaattacca caactcaccc aatatgaaat agataattgg gatagcctga taactactga 23460gaaaattgaa tttgtaattt taacactctt aaaacagaaa cattaaactt aatattttat 23520aaatattaga taaggtaatt atacccttcc ttaacaaata aaaacgacaa attattttgc 23580agctaaagag atgtatgtac tgtgaaaaat atcttcagaa aaatagaact ttgtttgaag 23640aataaggatt taaaaaatgt ttttaactct caagaagcaa atatctgggc ccagatggtt 23700tcactgaaga attctaccaa atgtttaatg aagaattacc accaactcta catagcatct 23760ttgagaaaac tgaagagaag ggaacatctc ccagttcatt ttatgaagtg ggtgttactc 23820tgatactaga actgtataag gacagctact cttgacacac tgcctatggg tagctctgct 23880ctgcaggaac agtcagaaaa aaaaaaaaaa gaagcactgg acaagggcag tataaaaaaa 23940gaaaactggg ccaggtgcag tggctcacac ctgtaatctc agcactttgg gaggctgacg 24000ctggtggatc acctgaggtc aggagtttga gactagcctg gccaacatgg taaaaccctg 24060tctctactaa aatacaaaaa ttagccaggc agggtggtgg ggaaaataaa aaggaaaaaa 24120aaacaaaaat aaactgcaga ccaatatcct tcatgagtat agacacaaaa ctccttaaac 24180tccttaacaa aatattagca agtagaagca atatataaaa ataattatac accatgatca 24240agtgggactt attccagaaa cgcaagtctg gttcaacatt tgaaaacaag gtaacccact 24300atatgaacgt actaaagagg aaaactacat aatcacatca atcaatgcag aaaaaagcat 24360ttgccaaaat ccaatatcca ttcatgatac tctaataaga aaaataagaa taaaggggaa 24420attccttgac ttgataaagc ttacaaaaga ctacaaaagc ttacagctaa cctatactta 24480atggtgaaaa actaaatgct ttcccctacg atcaggaaca aagcaaggat gttcactctc 24540attgctctta tttaacatag ccctgaagtt ctaacttgtg caaaacgata agaaagggaa 24600atgaaagacc tgcagattgg caaagaagaa ataaaactgt tcctgtttgc agatgacatg 24660attgtctcat agaaaatgta aagcaactag gggtaggggg gcagtggaga cacgctggtc 24720aaaggatacc aaatttcagt taggaggagt aagttcaaga tacctattgc acaacatggt 24780aactatactt aatatattgt attcttgaaa atactaaaag agtgggtgtt aagcgttctc 24840accacaaaaa tgataactat gtgaagtaat gcatacgtta attagcacaa cgtatattac 24900tccaaaacat catgttgtac atgataaata cacacaattt tatctgtcag tttaaaaaca 24960catgattttg gccaggcaca gtggctcata cctgtaatcc cagcatttta ggaggctgag 25020gcgagcagaa aacttgaggt cgggagtttg agaccagaat ggtcaacata gtgaaatccc 25080gtctccacta ataatacaaa aattagcagg atgtggtggc gtgcacctgt agacccagct 25140acttgggagg ctgaggcacg agaattgctt gaacaaggga ggcagaggtt gcagtgagct 25200gggtgccact gcattccagc ctggtgacag agtgagactc catctcaaaa aaaataaaat 25260aaagcatgac ttttcttaaa tgcaaagcag ccaagcgcag tggctcatgc ctgtaatccc 25320accactttgg gaggccgagg caggcagatc acaaggtcag gagtttgaga ccagcctgac 25380caacatggtg aaaccccatc tctactaaaa aatatataaa ttagccaggc atgtgtagtc 25440tcagctactc aggaggctga ggcaggagaa tcacttgaac ccggaggcag aggttgcagt 25500gttgagccac cgcactccag cctgggtgag agaacgagac tccgtctcaa aaaaaaaaag 25560caaaataacc taattttaaa aacactaaaa ctactaagtg aattcagtaa gtctttagga 25620ttcaggatat atgatgaaca tacaaaaatc aattgagctg gacaaaggag gattgtttta 25680ggtcagtagt ttgaggctgt aatgcacaat gattgtgcct gtgaatagct gctgtgctcc 25740agcctgagca gcataatgag accacatctc tatttaaaaa aaaaaaaatt gtatctctat 25800gtactagcaa taagcacatg ggtactaaaa ttaaaaacat aataaatact gtttttaatt 25860gcctgaaaaa aatgaaatac ttacatataa atctaacaaa atgtgcagga cttgtgtgct 25920gaaaactaca aaacgctgat aaaagaaatc aaagaagact taaatagcgt gaaatatacc 25980atgcttatag gttggaaaac ttaatatagt aaagatgcca attttatcca aattattaca 26040caggataaca ttattactac caaaatccca gaaaaatttt acatagatat agacaagatc 26100atacaaaaat gtatacggaa atatgcaaag gaactagagt agctaaaaca aatttgaaaa 26160agaaaaataa agtgggaaga atcagtctat ccagtttcaa gacttacata gctacagtaa 26220tcaagactgt gatattgaca gagggacagc tatagatcaa tgcaaccaaa tagagaacta 26280agaaagaagc acacacaaat atgcccaaat gatttctgac aaaggtgtta aaacacttca 26340acgggggaag atatgtctct cattaaaggg tgtagagtca ttgcacatct ataggcaaaa 26400agatgaacct gaacctcaca ccctacagaa aaattaactc aaaatgactc aaggactaaa 26460cataagatat acatctataa aacatttaga aaaaggccac gcacggtggc tcacgctcgt 26520aatcccagca ctttgggagg ccaaggcagg tggatcacct aaggtcagga gtttgagacc 26580agccggatca acatggagaa gccccatctc tactaaaaat acaaaattag ctggacgtgg 26640tggcacatgc ctgtaatccc agctacttgg gaggctgagg catgagaatc gcttgaaccc 26700ggggggcaga ggttgcggtg agccaagatc acaccattgc actccagcct gggcaacaag 26760agcaaaactc caactcaaaa aaaaaaaaaa aaaggaaaaa tagaaaatct ttgggatgta 26820aggcgaggta aagaattctt acacttgatg ccaaactaag atctataagg ccagtcgtgg 26880tggctcatgc ctgtaattcc agcactttgg tcaactagat gaaaggtata tgggaattca 26940ctgtattatt ctttcaactt ttctgtaggt ttgacatttt tttagtaaaa aattggggga 27000aagacctgac gcagtggctc acacctgtaa tcccagcact ttgggaggcc ggggcaggtg 27060gatcacacgg tcaggagttc gagaccagcc tggccaacat ggtgaaaccc cgtctctacc 27120aaaaatataa aaaattagcc gggtgtcatg gtgcatgcct gtaatcccag ctactgagga 27180ggctgaggca ggagaatcac ttgaacctgg gaggtggaag ttgcagtgag ccgagattgt 27240gccactgcac tccagccttg ggtgacagag cgagactccg tctcaaaaga aaaaaaaaaa 27300aaagaatatc aaacgcttac tttagaaact atttaaagga gccagaattt aattgtatta 27360gtatttagag caatttttat gctccatggc attgttaaat agagcaacca gctaacaatt 27420agtggagttc aacagctgtt aaatttgcta actgtttagg aagagagccc tatcaatatc 27480actgtcattt gaggctgaca ataagcacac ccaaagctgt acctccttga ggagcaacat 27540aaggggttta accctgttag ggtgttaatg gtttggatat ggtttgtttg gccccaccga 27600gtctcatgtt gaaatttgtt ccccagtact ggaggtgggg ccttattgga aggtgtctga 27660gtcatggggg tggcatatcc ctcctgaatg gtttggtgcc attcttgcag gaatgagtga 27720gttcttactc ttagttccca caacaactgg ttattaaaaa cagcctggca ctttccccca 27780tctctcgctt cctctctcac catgtgatct cactggttcc ccttcccttt atgcaatgag 27840tggaagcagc ctgaagccct cgccagaagc agatagtgat gccatgcttc ttgtacagcc 27900tacaaaacca tgagcccaat aaaccttttt tctttataaa ttatccagcc tcaggtattc 27960ctttatagca agacaaatga accaagacag ggggaaatca acttcattaa aataatctat 28020gcagtcacta aacaaataag aacaagaggc tccagaagtg ggaagccaat acccagagtt 28080cctacaatac agtatctgaa aagtccagtt tccaaccaaa aaatatatat atacaggccg 28140gacatggtag cttatgtctg taatcccagc actttgggat gctgaggcgg gcagatcacc 28200ctaggtcagg agttcgagac cagcctggcc aatatggcaa aaccccgtct ctactaaaaa 28260tacaaaaatt agccaggcat ggtggtggat gcctgtaatc ccagctactc gggaggctga 28320ggcagggaat cacttgaacc caggaggcag aggttgcagt gagccgagat cacgccactg 28380aactccagcc tgggcaacaa agtgagactc cacctcaaaa aaaaaaaaaa tatacatata 28440tatatgtgtg tgtgtgtgtg tgcgcgcgtg tgtgtatata cacatacaca tatatacata 28500tatacagaca cacatatata tatgaagcat gaaaagaaac aaggaagtat gaaccatact 28560ttctgtggtt atgataggat ggggtatcac gggggaagta gacaagggaa actgcaagtg 28620agagcaaaca gttatcagat ttaacagaaa aagactttgg agtaaccatt ataaatatgt 28680ccacagaatt aaagaaaagc gtgattaaaa aaggaaagga aagtatcata acaatattac 28740tccaaataga gaatatcaat aaaggcatag aaattataaa atataataca atggaaattc 28800cggagttgaa aggtagaata actaaaattt aaaattcact agagaaggtt caacactata 28860tttgaactgg cagaagaaaa atttagtgag acaaatatac ttcaatagac attattcaaa 28920tgaaaaataa aaagaaaaaa gaatgaagaa aaataaacag aatctcagca aaatgtggca 28980caccattaat cacattaaca tatgcatact gagagtaccg gaagcagatg agaaagagga 29040agaaaaaata ttcaaatgat ggccagtaac ttcctagatt tttgttttaa agcaataacc 29100tatacaatca agaaactcaa tgaattccaa gtaggataaa tacaaaaaga accacaaaca 29160gatacaccat ggtaaaaatg ctgtaagtca aaaacagaga aaatattgaa agcagctaga 29220ggaaaactta taagagaacc tcacttacaa aagaacatca cttataaaag aaccacaata 29280atagaaacag ttgacctctc atcagaaaca atgaatgata acatatttga agtgctcaaa 29340gaaaaaaaat aaagattcct atatacgaca aagctgtctt tcaaaaatat acatccaaaa 29400ggattgaaac cagggtcttg aagagttatt tgtacatcca tgttcatagc agcattattc 29460acaatagcca aaaggtagaa gcaacccaag ggtccatcga caaataaata aaatgtggta 29520tatgtataca caatggaatt tattcagtat taaaaaggaa tgaaattctg acacatgcta 29580caacatggct aaaccttgag aacactatgc taagtgaaat aagccagcca caaaaggaca 29640aataccatat tacttcactt gtatgaaata cctagggtag tcaaattcag agatagaaag 29700taaaacagtg gttgccaagg gctgagggag ggagtaacgt ggagttattg ttgaatgggt 29760acagaatttc agttttgcaa gataaaaaga gttctggaga cagatggtgg tgagggtggt 29820acaacaatac aaatatactt tatactactg aacagtatac ttaaaaatga ttaacatggt 29880gaaaccccgt ctctactaaa aatacaaaaa aattagctgg gtgtggtggc gggcacctgt 29940aatcccagct acttgggagg ctgaggcagc agaattgctt gaaaccagaa ggcggaggtt 30000gcagtgagct gagattgcgc caccgcactc tagcctgggc aataagagca aaactccgtc 30060tcaaaaaata aaaaataaaa aaaatttaaa aatgattaag caggaggcca ggcacggtgg 30120ctcacaccta taatgccagc actttgggag gccgaggcag gcgatcactt gagaccagga 30180gtttgagacc agcctggcca acatggcaaa accctgtctc tgctaaaaat acaaaaatta 30240gccaggcatg gtggcatata cttataatcc cagctactgg tgagactgag acacgagaat 30300tgcttgaacc caggaggcag agattgcagt gagtcgagat cgcgccactg aattccagcc 30360tgggcgacag agcaagattc tgtctcgaaa aaacaaaaac aaaaacaaaa agcaaaacca 30420aaaaataatt aagcaggaaa cgagattgct gctgaggagg agaaagatgt gcaggaccaa 30480ggctcatgag agcacaaaac ttttcaaaaa atgtttaatg attaaaatgg taaattttat 30540atgtatctta ccacaaaaaa aagggctggg gggcaggaaa tgaaggtgaa ataaagacat 30600cccagagaaa caaaagtaga gaatttgttg ccttagaaga aacaccacag gaagttcttc 30660aggctgaaaa caagtgaccc cagagggtaa tctgaattct cacagaaaat tgaagcatag 30720cagtaaaggt tattctgtaa ctatgacact aacaatgcat attttttcct ttcttctctg 30780aaatgattta aaaagcaatt gcataaaata ttatatataa agcctattgt tgaacctata 30840acatatatag aaatatactt gtaatatatt tgcaaataac tgcacaaaag agagttggaa 30900caaagctgtt actaggctaa agaaattact acagatagta aagtaatata acagggaact 30960taaaaataaa attttaaaaa atttaaaaat aataattaca acaataatat ggttgggttt 31020gtaatattaa tagacataat acaaaaatac cacaaaaagg gaagaagaca atagaactac 31080ataggaataa cattttggta tctaactaga attaaattat aaatatgaag tatattctgg 31140taagttaaga cacacatgtt aaaccctaga tactaaaaag taactcacat aaatacagta 31200aaaaaataaa taaaataatt aaaatgtttg tattagtttc ctcagggtac agtaacaaac 31260taccacaaat tgagtggctt aacacaactt aaatgtattt tctcccagtt ctggaggcta 31320aacacctgca atcaaggtga gtacagggcc atgctccctg tgaaggctct aggaaagaat 31380cctcccttgt ctcttccagc ttccagtggt tctcagtaac cctaagtgct ccttggcttg 31440tagctatatc attcctagca accagaaaga agaaaataat aaagattatg gcaaaaaata 31500atgaaatcaa aaggagaaaa atggaaaaaa ataaataaaa ccaaaagcta gttctttgaa 31560aagatcaacc aagttaacaa accttttaac tagactgaca aaaaggaggt aagactcaaa 31620ttactagaat cagaaataaa agaggggaca ttactaatga gggattagaa aagaatacta 31680cgaacaaatg tgtgccaaca aattagaaaa cttagatgaa atggacaggt tcctaggaca 31740acatcaacta ccaaaattta ctcaagaaga aagagacaat ttgaatgagc tataacaagg 31800gaagagactg aattgacaac caagaaacta tccacaaaga aaatcccagg cccagaagat 31860ttcactgtga aattctttca aacttataaa tataaattaa catcagttct tcacaaactc 31920ctccaaaaaa aagaacagat ctctatttac aggcgatacg atctttagaa aatcctaagg 31980gaactactaa gacactatga taactgataa acaagttcag caaggctgca ggatagaaaa 32040ccaatataca aaaatctatt atatttctat acacttgcag tgaacaaccc aaaaatgaga 32100ttaagaaaat aattcaattt acaataacat caaaaagaat aaaaacactc aaaaataaat 32160ttattcaagt aagtgcaaaa cttatactct agaagctaca aaacactgtt aaaagaaatt 32220aaaggtttac ataaatgaaa aactatccca tgttcatgga tcaaaagact tattactggc 32280aatgctctcc aaattgatct ataaattcaa caaaatcctt atcaaaatcc cagatgaggc 32340tgggggtggc ggttcatgcc tgtaatccca gcactttggg aggctgaggc acgcagatta 32400cctgaggtcg ggagctcgag atcagcctga ccaacatgga gaaaccctat ctcttctaaa 32460aatacaaaat tagtcaggcg tggtggcaca tgcctataat cccagctact cgggaagctg 32520aggcaggaga atcgcttgaa cccaggaggc agaggttgca gtgagccaag atcgtgccat 32580tgcactccag cctgggcaac aagagcaaaa ttccatctca aaaaaaaaaa aaaaaaaatc 32640ccagatgact tcactgttga aattgaaaag attattctaa aattcacatg gaattgcaag 32700accttgagaa tagccaaaac aaacttgaaa aacacgaaca aaatatagga tgactcactt 32760gccaattgca aatgttacga cacagcaaca gtaatcaaga ctgtgtggta ctggcaaaag 32820acacatacat acatacatat caatggaata taattgagag tacagaaaca agcctaaaca 32880tctatggtaa gtgcttttct atttttttct tttttttttt cttttttgta gagatagaat 32940ctcaccatgt tgcccaggct ggtcttcaac ttctgggctc aagcaatcct cccactgtgg 33000cctcccaaag tgctgggata actggcatga gccaccacat ccagcccaga tgattttcaa 33060aaaagtcaac aagaccattc ttttcaacaa ataggtctgg gatgatcaga tagtcacatg 33120aaaaaaaaaa tgaagttgga ccctccatca cactaaagtg ctgcgattat aggcatcagc 33180caccacatcc agcccaaatg attttcaaaa aggtcaacaa gaccattctt ttcaacaaat 33240aggtctggga taatcagata gtcacatgaa aaaaaaaatg aagttggacc ctccatcaca 33300ccatatgcaa aaattaattc aaaaatgaat tgatgactta aacgtaagag ttacgactgt 33360aaaactctta gaaggaaaca tacgggtaaa tcttaaagac gttaggtttg acaaagaatt 33420cttagacatg acaccaaaag catgaccaac taaggtaaaa tagggtaaat tgtacctacc 33480aaaatgaaaa acctttgtgc tggaaaggac accatcaaga aatggaaagc caaaatagcc 33540aaggcaatat taagcaaaaa gaacaaagct ggaggcatca tactacctga cttcaaagca 33600acagtaacca aaacagcatg gtactagtag aaaaacagac acatagacca atggaacaga 33660ataaagaacc caaaaataaa tccacatatt tatagtcaac tgatttttga caatgacacc 33720ccttcaataa atgatactag gaaaactgga tatcgatatg cagaagaata aaactagacc 33780cctatctctc accatataga aaaatcaact cagactgaat taaagacttg aatgtaagac 33840ccaaaactat aaaactactg gtagaaaaca taaggaaaaa cgcttcagga cattggtcca 33900ggcaaagatc ttatggctaa aacctcaaaa acacaggcaa caaaaacaaa aatggaaaaa 33960tagcacttta ttaaactaaa aagctcctgc acagcaaagg aaacaacaga atgaaaagac 34020aacctgtaga atgggagaaa atatttgcaa actatccatc catcaaggga ctagtatcca 34080gaacacacaa gtgactaaaa caactcaaca gcaaaaaagc aaataatctg gtttttatat 34140gggcaaaaga tctgaataaa cattctcaaa ggaagacata caaatgtcac tatcattctg 34200ccagtaccac actgtcttga ttacttgtta gtgtataaat ttttaaattg ggaagtgtga 34260gtcatcctac actttgttct tgtttttcaa gtttgttttg gctattctgg gagccttgca 34320agtataaaat agccaacaag tatgaaaaaa tgctcaccat cactaatcat cagagaaata 34380aaaatcaaga ccactatgag atatcctctc actccagtta gaatggctac tatcaaaaag 34440acaaaatata atggatgctg gcaaagattt ggagaaaggg gaactcctat acactgtggg 34500tagggatgca aattggtaat ggccattatg gaaaataata ctgaggtttt tcaaaaaact 34560gaaaatagaa ctaccatatg atccagcaac cctactactg ggtatttatc caaaggaaag 34620aagtcagtat actgaagaaa tatatgcact ctcatgttaa ttgcaacact gttcacaaca 34680gccaagacag ggaataaatc taaatgtgca tcaacagatg aatggataaa gaaaatgtgg 34740catatacact caatagaata ctattcagcc attaaagaag aatgaaatcc tgtcatccca 34800gcaacatgga tgaacctgga ggacattata tttaatgaaa taagtaaagc acaaaaagat 34860aaacagtaca tgttctcact cagacatggg tgctaaaaag aaaatggggt cacagaatta 34920gaaggggagg cttgggaaaa gttaatggat aaaaatttac agctatgtaa gaagaataag 34980ttttagtgtt ctatagaact gtagggcgag tatagttacc aataacttat tgtacatgtt 35040caaaaagcta gaagagattt tggatgttcc cagcacaaag gaatgataaa tgtttgtgat 35100gatggatatc ctaattaccc tgattcaatc attacacatt gcatacatgt atcaaattat 35160cactctgtac ctcataaata tgtataatta ttacgtcaac aaaaaaagga aaaaaaagaa 35220aattaagaca acccacataa tggaagaaat aaaatatctg caaattatat atatctgata 35280aatatttaat atttataata tataaagaac tcctacaact caagaacaac aacaaaacaa 35340cccaattcaa aaatgggtaa aagccttgaa tatacactta tctaaagact atatacaatt 35400ggccaataaa gacacgaaaa gatgctcaac atcactagtc atcagggaaa tataaatcaa 35460aaccacaatg tagaatgtag acaccacttc atatgcacta ggatggctag aataaaaagg 35520taataacaaa tgttggtaag gatgtgaaaa aatcagaaac ctcattcgct gctgttggga 35580atgtaaagtg atgcagccac tttggaaaac agtctggcag ctcctcaaat tattaaatac 35640agagttaccg tatgacccag gaatattcct cctgggtcta taaccaaaaa aatgaaaaca 35700tatatccaca taaaaacttg tacatgggca tttatagcaa cattattcat aacagcaaag 35760gtggtaagaa cccatatgcc catcatctga tgaacaggta aataacatgc ggtattatcc 35820atacactaga atattatctg cccatacaag gagtgacatc cagctacatg ctacaaggat 35880gaatctcgga aaccttatgc taagtgaaag aagccagtca caaatgacca cagattatga 35940ttccatgcat cggaaatgac cagaataggg aaatctatag agacagaaag tagattagtg 36000gttgggtggg gctgggagga caggtagtac actactttcc cagaactact ggaacaaagt 36060accacaaact ggggagctta aacatagaaa ttgatttcct cacagttctg gagactagga 36120ctctgagatc aaggtgtcag cagagctggt tctttctgag ggccctgagg caaggctctg 36180tcccaggcct ctctccttgg ctggcaggtg gccatcttct ccctgcgtct tcacatcatc 36240ttttctctgt gtgtgcccat gtccaaattt tgattggctc attctgggtc atggccaatt 36300gctatgcaca aagtgaagtc tacttccaaa agaagggaag agggaacact gactaggcta 36360aacttatagt cattttaatg tccgcttttc ctatgagatt gtgaacacac agaagtaggg 36420tttttatcta cattgtgcaa agtttaataa gaaaaataga attcaagaga agcagttcaa 36480tagcaggaat ttaatatggg aactaattac aaggtttagg gcaggactaa aaagccagtt 36540gggatggtga gccaacccag agattagcaa cagtgggacc ccatctacct accacccatg 36600aagctggaag gataaaggag gggctattat cagagtccac aagccagtgt cagagtcctt 36660ggctggagct gggaccaccc tagagacact gtgcaaagca gaaaacaagg gggaaaaacc 36720ctgacttctc ccttcctccc acctttcaat ctcccactag tgcttcctac tagccatact 36780tggccagaga cagtgacaag gaacactgca aaatgaagtt tgtaggaatc atctccctct 36840gagacagaga aatatggaag ggtagaaaat gaatcagagg ataaagagaa aaaaccctga 36900gtactatctt atttatcttt gtatctccag tgcctaatct gtctctcaaa aaaggaaagc 36960aattgagaga aactgaaaac tccaattgaa atgaaagaat ggagaattac tggactagaa 37020gagaagagaa aaatttattc cgcatagagt aaacaagaat ggattcacaa aggacgtgat 37080gaatgaaaag ctataatcag caaagatttg ccagagaaat taaaaagtgg taaactcagc 37140cacgctgtac aacctgaagg cacaatgcat gaaaacgttt caagaaatga caagatttga 37200agtcaaattc taagtgcttt tccagaatct ctcaagacga ttatatagct accccatttt 37260attaaataaa atggaaactt actaaacttt ccccttgtat taaactaaca tatgtcctaa 37320tagcaaacga ttctggaatt cctagagtaa aatatatttc gtcaaagtgt attgctcttt 37380taatattctg ctgacctcct tttgctattt aggatatttg tatacacatc acacgtaaat 37440ttggtctata gtttacatct acgggcttat actgttcttt ttttcatttt tttaaaattt 37500ccaaccccca gtatccatat actgctctct atcagggtta ttttaacttt gtaaaatcag 37560ctgagatgct ttccatgttt ttttttttta ttttctgcca catttgaata gcataggagt 37620taccaccatc aaccttggat tatttaagca ttcacgattc cacgtgtgga ttttttattc 37680agagtctttc ttgtcattcc tgctatcagc acagaaccca atctcagctt tccagctata 37740ctctcacccc atggaatttg cagatgaagt tcaaaaggac ctttgcatta tcctgcctcg 37800ccctcttccc ccttcattta gacatcacct tcttctagaa cgtcttacct gacatgccct 37860gctcccaacc cctgctgccc aattgtgtgc tctcccgtgt cctggcctgc catcctcttt 37920agtaattgcc tgctccctca tctgtctccc cacccagaca ttaagctgaa tagactggat 37980ttgtgtcttg tccatcacta taatctcagc acctagtacc tagtaggtac ttaccatgta 38040ttcattagca aaatgttatg tataaccttg caccttaaaa acaagagaag gaagacaaaa 38100ttaagtctta agactatggt ttagaacatg gatcagaaac tacagtctgc agcccaaatc 38160cagaccaaat gaagagacca tgttcattta catacaacct atagcagctt tcacactaca 38220ggagcagagc taagtagttc caagggaaca cacggccctg caaagcctaa aatatttact 38280ctatagctct tcacagaaaa agttttcaga tccctcgttt agaactcttg ttcatatgca 38340atttcactaa accatagttt tttgggtttg tttggttttt tttggcaaaa aggaatgagc 38400cgatccagaa aaggttgaaa agaatgaatc attactgctg aaagaatgtg cacacagtcc 38460gtcagtattc tgctgccatg ctgacaccca tccaatagtg tcatgagatg cagcagctac 38520tactgtgttc tcaatgccga gtccacccac tccataacca tgtccaagca atcttgggaa 38580catcatcacc atgcttgttt atccttaagg tattgcctca catacagcag tggctggtca 38640taaagtcaaa tgacactagt ggccaggagg tcaagagaat gagtgaggac aggtgggtag 38700gcagcccagg ccctagcaac agcaggagct cacccctcag tcactctagc caggactgaa 38760atacttttca ccctttcaag agagactagg aatctggatt tttatgtgaa atatcttgat 38820tactaaatgt tgtcaacaga catgtcaaaa ggtaaaacta agtaagttca tggggcagat 38880tgactattca ggttatagaa ttaaggattc ttatccaaca cagataccaa ccaaaaagct 38940gacgtataac atattaggag aaactatgtg cactgtcgaa acatcaacaa ggggctaatg 39000tctaaaatag tctatattgg attccagttg aaacatgggg aaaggacatg aacaggcaac 39060ttatgtcaat ggaaactcaa aaagataaca agcatatata aaagcattct caaattcagt 39120agtaaacaga cagatgcaaa taaaaagagg gaaactgctg ccgggcacag tggctcacac 39180ctgtaatccc agcactttgg gaggccgagg cgggcggatc atgaagtcag gagatcgaga 39240ccatcctggc taacatggtg aaaccccgtc tctactgaaa acacaaaaaa ttagccaggc 39300gtagtggtgg gcaccagtag tcccagctac tcaggaggtt gaggcaggag aatggcatga 39360acccaggagg cggagattgc agtgagccga gaccatgcca ctgcactcca gcctgggcga 39420ctgagtgaaa ctccatctca aaaaatataa taataattat aattataata ataataaata 39480gtaaataaat aaaaagagag agactgctaa agtctagaaa gttgaatgat gccaagcgca 39540tgcaaagatc agggccttgg gatggccggg tgcagtggct cacgcctgta atcccaccac 39600tttgggaggc caaggcgggc ggatcatgag gtcaagagat caagaccatc ctggccgaca 39660cagtgaaacc cggtctctac taaaagtaca aaaaaatata tatatatata tatattatta 39720tattatatat atatatatca gagccttggg aatccttgtg tgctgctggg gaaggtagtg 39780gtgcagccac ccttgacagc aatctggcag tacttggtta tattaagtat aggcacacac 39840cacgaccagg cagtcctact cctgggtcta aatcccaaag aattctcaca caagtccata 39900aggagacatg tacgaggctc attcagcatt actgggagtg ggaatcaacc tgggtgtcca 39960tctacaggag acgagatgga caaaatgtgg tggatattaa gaccagaatc accaagtaac 40020agagatgggt ggtgagtgac aatcctaaga tacagaataa aggctagaac atgatgccat 40080tcatgtaaat taaaaataga tgcacacaaa gcagtatacg cgtgaccctt gaatagcaca 40140ggtttgaact gcctgtgtcc acttacatgt ggattttctt ccacttctgc tacccccaag 40200acagcaagac caacccctct tcttcctcct ccccctcagc ctactcaaca tgaagatgac 40260aaggatgaag acttttatga taatccaatt ccaaggaact aatgaaaagt atattttctc 40320ttccttatga ttttctttat ctctagctta cattattcta agaatatggt acataataca 40380catcacacgc aaaataaatg ttaattgact gtttatatta tgggtaaggc ttccactcaa 40440cagtaggctg tcagtagtta agttttggga gtcaaaagtt atacacagat tttcaactgt 40500gcaggcaatc agttcccctg accccctcat tgttcacggg tcaactgtat atacacaaaa 40560gtattatatg aacctcatta gaatagctgt ctatagggag aagagaatga gagtgggata 40620aaacggaatg aacaaataaa ccaacaaatg cattaacaag caaaacaaca gaggggcttg 40680catgggccag tgatgataaa gggctaagaa tgagaatata attaattcaa ttcctcacac 40740ctgaggtcta aaaccaagga aagggagggc caggcgtgga ggctcacgcc tgtaatccca 40800gcactttggg aggctgaggc gggcggatca caagattagg agtttgagat cagcctggcc 40860aacacagtga aagcccatct ctacaaaaaa tacaagaatt acccaggtgt ggtggcacat 40920gcctgtagtt agctactctg gaggctgagg caggagaatc acttgaaccc aggaggcgga 40980ggttgcaggg agccgagatc acaccattgc actccagcct gggtgacaga gtaagactct 41040gtctcaaaaa aataaaaaaa ataaaaaaac agagaaaggg aggaaactag atccaggctg 41100actagataca gcctttagag ttagaaaaga tgatttgaca atctaagccc acactcagat 41160tgaatgaaat tgaaaagcct ttcaaactaa aacatttaat tacaccatct gctgcagaca 41220gaactcagac aactcaaaca ggtaatgtca gcgtggtgtt ttatatcacc accctcaaca 41280cagaataaaa atcagctgca tgtgaagcag tgactagaat gaagaaaagg ctgcttctta 41340cttccttcta gtggttcttt ccgaaaacat taataggcac cagctctatg catgtcaccc 41400tgcagggaga catggggtat ataactatga cttactgttc attcctcaag gaattcccaa 41460tcttgtggaa gattatacac aatgaggcaa caaaaactat ccaataaaac cacggaaaag 41520aagccagtga caaagaagcc agtgatgaaa ggccctgtga gcagagctga tggccatttg 41580gggaagaaag accaacatgg atgggggtga tcagggtggc tccgtgggaa agctggaaga 41640gaagtggcag atctctgagc tggatgatgg gccactacca tctgtatatg gctaattaaa 41700gaccatgtgt ggatttttta ttcagctctt tcgtgtcatt cctgctatca gcacagaacc 41760caatctcaac tttccagcta tattgagcta aacttctcac ctcatggaat ttgcagataa 41820agttcaaaag gatccttgcc ttttcaaaat aattttgaat ggttgagtag tccctctgtg 41880ctctctcact gacaccctct caaggctgct gagcacgtgc catgctatgg ctttctccaa 41940catcaggaaa tgttctccac tcagtttcac cttaatacaa atgtgttctc tcttcagaga 42000aggcaaaaaa attcatgacc atctgactgg gagaagtcat ttctaggtaa agtgtccatc 42060tttttctgag gaacacagga ggaaaatctt acagaaaaga gttaacacag caggcctaag 42120actgcttttt aaaataaata aataaataaa taaataaata aataaataaa taaataaata 42180aataaatgaa tgatagggtc ttctgtattg gccaggctag tctcaaattc ctggcttcaa 42240gagatcctcc caccttggtc tcccacagtg ttgggattat agacatgagc cattgtgctt 42300ggcccaagac tgttattctt aaaaagtctc ataaaaagca tggttaatcc ttggctggca 42360cctgggaact tagatttcag aagggttccc accatccaac ctggaaagag ggactcactg 42420tgcctaaatt attgtgtggt ttatgctgaa ctcctgcttt tcttcaggta gcgtggaatg 42480tggtatgtgc tgggcaaagg gggcctgcat gaccagcccc caataaaaac cctgggtgtt 42540gggtctctag tgagtttccc tggtagacag catttcacat gcgttgtcac agctccttcc 42600tcggggagtt aagcacatac atcctgtgtg actgcactgg gagaggatgc ttggaagctt 42660gtgcctggct tcctttggac ttggccccat gcacctttcc ctttgctgat tgtgctttgt 42720atcctttcac tgtaataaat tacagccgtg agtacaccac atgctgagtc ttccaagtga 42780accaccagat ctgagcatgg tcctgggggc ccccaacaca gaaataaatt ataaaagacc 42840aaggactggg catggtggcc catgccggta atctcagcgc tttgggaggc cgaggcagga 42900ggaccagtta agcccaaaag ttcaaagtta cagtgaccta tgactgcgcc aatgcactct 42960aacctgggag acagagcaag accctgtccc caaaacaata aactaaacac atacttctgc 43020cttccaagtg tcttaaaatt caatggaatg gtagaaacat ttttaaaaca ctaaatcaaa 43080agaaacctgg aaaacaagag tgccgatggc caactaaaat gtctaggaaa tttctgaaaa 43140gtaaaaagta ctcagaacca gattacctga gcaaaccata gcccaataca agcttgggag 43200gaggctgtta tgcagaagga aatggtaaca ggtttccagg aacagacttg taacagcaga 43260tagaacagca gaggtagaac ctgacaaggt gattacctgg ggaactgcag tctgaatgac 43320caggactgtt ggacccttcc cctcacatgg aatacacacg ccactcagca gcacaccaca 43380gctcttcaac aatcacagga ggcacgctac gcctagtaag acaggaaaaa aggaattctc 43440aaacttcgaa gatgaacaca taaagaatca ccaagttttt attcagtatg atgaaacagg 43500gacactgaat caacagaaca caaacccaag caaagataat tactagagca catagaagaa 43560attattagat attcttggga agacctaagg ggacattata aagagcaagc agttggtatg 43620tgacgatctt tgtgatatac caagaaataa aaacacagga tgaagaccag atagagaata 43680atgctactat ttgtgcaaaa aaggagaaat ggagaatctg attcatattt gcttgtattt 43740gcatgaagaa actttggaag gtacataagt aactaacaac aatggttacc tacttgtaag 43800gcgagagaag taagaggaca ggaatggtgg gaacaccttt tgtgtccgga attggtgggt 43860tcttggtctg acttggagaa tgaagccgtg gaccctcgcg gtgagcgtaa cagttcttaa 43920aggcggtgtg tctggagttt gttccttctg atgtttggat gtgttcggag tttcttcctt 43980ctggtgggtt cgtagtctcg ctgactcagg agtgaagctg cagaccttcg cggcgagtgt 44040tacagctctt aagggggcgc atctagagtt gttcgttcct cctggtgagt tcgtggtctc 44100gctagcttca ggagtgaagc tgcagacctt cgaggtgtgt gttgcagctc atatagacag 44160tgcagaccca aagagtgagc agtaataaga acgcattcca aacatcaaaa ggacaaacct 44220tcagcagcgc ggaatgcgac cgcagcacgt taccactctt ggctcgggca gcctgctttt 44280attctcttat ctggccacac ccatatcctg ctgattggtc cattttacag agagccgact 44340gctccatttt acagagaacc gattggtcca tttttcagag agctgattgg tccattttga 44400cagagtgctg attggtgcgt ttacaatccc tgagctagac acagggtgct gactggtgta 44460tttacaatcc cttagctaga cataaaggtt ctcaagtccc caccagactc aggagcccag 44520ctggcttcac ccagtggatc cggcatcagt gccacaggtg gagctgcctg ccagtcccgc 44580gccctgcgcc cgcactcctc agccctctgg tggtcgatgg gactgggcgc cgtggagcag 44640ggggtggtgc tgtcagggag gctcgggccg cacaggagcc caggaggtgg gggtggctca 44700ggcatggcgg gccgcaggtc atgagcgctg ccccgcaggg aggcagctaa ggcccagcga 44760gaaatcgggc acagcagctg ctggcccagg tgctaagccc ctcactgcct ggggccgttg 44820gggccggctg gccggccgct cccagtgcgg ggcccgccaa gcccacgccc accgggaact 44880cacgctggcc cgcaagcacc gcgtacagcc ccggttcccg cccgcgcctc tccctccaca 44940cctccctgca aagctgaggg agctggctcc agccttggcc agcccagaaa ggggctccca 45000cagtgcagcg gtgggctgaa gggctcctca agcgcggcca gagtgggcac taaggctgag 45060gaggcaccga gagcgagcga ggactgccag cacgctgtca cctctcactt tcatttatgc 45120ctttttaata cagtctggtt ttgaacactg attatcttac ctattttttt tttttttttt 45180tgagatggag tcgctctctg tcgcccagac tggagtgcag tggtgccatc ctggctcact 45240gcaagctccg cctcccgggt tcacaccatt ctcctgcctc aacctcctga gtagctggga 45300ctacaggcaa tcgccaccac gcccagctaa ttttttattt tatttttttt ttagtagaag 45360cggagtttca ccatgttagc cagatggtct caatctcctg acctcgtgat ccatccgcct 45420cggcctccca aagtgctggg attacagacg tgagccactg cgccctgcct atcttaccta 45480tttcaaaagt taaactttaa gaagtagaaa cccgtggcca ggcgtggtgg ctcacgcctg 45540taaccccagc actttgggag gccgaggcgg gcggatcacg aggtcaggag atcgagatca 45600tcctggttaa cacagtgaaa ccccgtcgct actaaaaata caaaaaatta gccgggcgtg 45660gtggtgggca ccggcagtcc tcgctactgg ggaggctgag gcaggagaat ggcgtgaacc 45720tgggaggcag agcttgcagt gagccgagat agtgccattg ccttccagcc tgggcgacag 45780agcgagactc cacctcaaaa aaaaaaaaaa aaaatagaga cccggaaagt taaaaatatg 45840ataatcaata tttaaaaaca ctcaagagat gggctaaaga gttgacggaa caaatctaaa 45900tattagattg gtgacctgca aaaccagccc aaggaacatc ccagaatgca gcccataaag 45960ataaagagag catttccgct gggcacagtg gtatggcagg ggaattgcct gagtccaaga 46020gttgcaggtc acattgaacc acaccattgc actccaggcc tgggcaacac agcaatactc 46080tgtctcaaaa aaaaaaaaaa ttaaattaaa aaagacagaa tatttgagag aaaaaaatgc 46140ttatttcaag aaacatgaaa gataaatcaa gatattctaa ttcccaagta agaataattc 46200cagaagcaga aaatagaata gaggcaagga aacactcaaa acttctccag tgccatagaa 46260atgtgtatta atctttagaa tgaaacggac taccaaatgc tgagcaggaa gaacaaaaga 46320gatccactct taagccagtg tggtgcccaa gcgcagtggc tcatgcctgt aatcccagca 46380ctttgggagg ccgaggcagg tggatcacct gaggtcagga gtttgagatc agtcaggcca 46440acatggtgaa accctgtctg tactaaaaat acaaacatta gctgggtatg gtggtgcaca 46500tctgtaatcc caactacttg ggaggctaag gcaggagaat cacttgaaac caggaggtgg 46560aggttgtagt gagccgagat catgccacac tcccagcctg ggtgacagag caagattcca 46620tctcaaaaaa aaaatccact cctagacaaa taatagttaa attttagaac accaaggaga 46680aagaaaaaaa attgtaaagc ttcagagaaa ataaacatta actacaaaga aacgagagtc 46740agacgcgtgc acttcttcct agataccagc agataaagca atatctccaa aattcagaag 46800gttttaacgt agaatcctat acccagtcaa gaatattcac atggaaaagt gaaataaaaa 46860acattgttta aacatgcaag ggttcagaaa gtttaccatt cacagaatcc ctgaaaacaa 46920aaccaaataa tcacttaagg actcattaag aaaacaaatg aaataaaagc accaatgatg 46980agtaaataat cagaaaaatt tacagtttac ctaaataact gtttatgcat aatgtatgaa 47040aacccaaaaa tttaatatgg gacagaatta aaatcatgat aagattcttt tttgctttac 47100tcatggagag ttcacataaa cagattatct tttaatagca agagaaaaaa atgtttagat 47160atgtgtgaaa aactaagggt accaaaacag tgcaaattca tttatcatca ggaaaatcca 47220aattaaaacc acagtatcca ccagaataac taaaaggtaa aagacagaaa ttaccaagag 47280ttggcaagaa tgtggagcaa ccacatatac ttctggggta aataagttgg tgcaaccggt 47340actgaaaact gtttgctagt atctactaaa accgagcaca tgcacagact acaaccaagc 47400agttccactc ccagatacac actcaacaga aatgcacaca ctcactcaac aaaagacgtg 47460tactagagtg ttcatgtact tactattcat aatagtccaa aaatgcaaac aaccaactgc 47520caatcaaagt caaatgtata tctatattag ggatatatac aatggcatat acacagcaat 47580gagaatgaaa tgaaccagct cggcacagtg gttcatgcct gtaatctcag cactttgggc 47640gggtaaggca ggcagatcac ttgaggtcag aaatttgaga ctagcctggc caacacggtt 47700aaaacctgtc cccactaaaa acacaaaaat tagccgggca tagtggttgc aggcctgtaa 47760ttccagctac tcgggaggct gggttgggag aatcgtttga acccgaaagc cggaggtcgc 47820agtgagcgga gatcgtgcca ctgcactcca gcctggacga tagagcaaga ctccgtctca 47880aaaaaggaaa tcaaaaatat aaaataagat gacaggaata atccgcaaaa gatcagtaat 47940caaaataaat ataaatgggc taaagctacc tattaaaaga caaagatttc acacccataa 48000ggatagctac tatcaaaaaa agagagagaa taacagatgt tagcaaggat gtatggaaac 48060tgaaattctc acgcattgct ggtgagaata taaaatggtt cagcctctgc ggaaaacact 48120atgctgggtc atcaaaaaat taaaaataga agtactactt gatccaacaa ttctacttct 48180gggtatatac ccaaataact gaaagcaggg tcttgaagag atatttgtac acccatgatc 48240atggcagcat tattcataat agctatgatg tggaaccaac ataaatatcc tttgataaat 48300atatggataa gcaaaatgtg gtgtatacat tcaatggaat attaattagc aataaaaatg 48360aagaaaattc tgacacatgc tacaacatgg atgaaccttg agggcattac attaaatgaa 48420ataagccagt tataaaaaga caaatactat atgaggtact atattagata ctcatgcaag 48480gtacctaaaa taggcaaatt catagagaca aaaagcagaa tggtggttgc caggggctgc 48540ggtaatggat acagagcttc aattttgtaa gatgaaaaaa ttctggagat tggttgcata 48600acaatgtgca cacacttaac actggggaac tgtaaactta aaagtagtaa atggtaaaaa 48660taaaaataat aaataataaa ttttatgtta ttttaccaca atatttatta aaagacaaag 48720attaactaat taaacaaaat ccagccataa gctaatggta agagtaacaa ttaaagaaga 48780cacagaaaat tgaaaatcag tgactagaaa aagatattcc atataaatgc taacaaaaag 48840caagtacagc aatataaaga gaatgaacaa aaaaaaaatt aaataagatg gctcgtttat 48900tcccaaaagg tacaattcac caagaagata caagaattgt gaacctttaa gcacataaaa 48960cagcttcaaa aatacaacat ttaaagaaaa atatatatta aacatagaaa tagtacaaaa 49020acccctacaa gaatcataat gggagtcttc aatacaactc tccatatcaa caggtcaaac 49080agagaaaaaa aataagttaa ggatgcagaa aacctgaatt accatcaata aacttgagat 49140taatatagaa ctgtataccc aatatactaa gagttcaggg aacagtcgtg actgacagtg 49200gactgcaaat taatctgttc ttaatctttg tttttctttc agcactgtgg cagaatagag 49260atcctaaaaa ccttccagct acaaaacatc tttttaaaaa tataaaaaaa tacaaaaata 49320actctgaaat caatagaaga cacatggtga aaccaaaatt ctagaataca gggagaataa 49380aggcattttc agatattaca aaaacagaaa attgatcatt gctgaagtaa tttctaaaga 49440atgtacttga gggagaagaa aaatgttcca aagaaaagta tctgtgatac aagaaggaat 49500ggaaagtgaa gaaatggtaa acaggtagat aaagctaata aatgttgacc tagaaaataa 49560caaaaacaat agcaataatg tctcgttgga agggttgaag taaaaataca attaaggcca 49620aatgtgaggt aagtggaatg aaagaattag aagtccttgc cttgttcaca ggactgatta 49680aataaatgag ccaggttttc cattcaaaca gttaaaactt gaacaaaata aactcaaatt 49740aagtagaaag ataaaaaaca gaaattaatg tcatagaaaa ataaaaaatc aatagaatta 49800atcaataaat cctggttaat aaaagctggt tctttgaaag gattaataaa ataatcatta 49860agcaagtctg atcaaaaaaa aagagaaaag gtaccaaaaa aagtactgta tcagaaagag 49920aacatacaga tacatacaga tatgtaagag tctgttttct tacaccagaa tactatatac 49980aacattatgc tagcatatat taaatttcaa taatgttaat gattttctag gaaaacagaa 50040aatattaaat ttactttgaa gaaacagaaa aactgagaaa aataaatgat catgaaaaaa 50100atgaaaaggt aattaaatac tgatattaac tgcctaaaca acaccagcag cagcccaggc 50160agtctgcagt caagttctgc caaacttgag ggaacagata attcttctat tccagagcat 50220agaaaatgat ggaaagtttc ccaatttaat cagagaggac agcctgatcc ttgttatgaa 50280cacagataaa aatggggtaa actatatgcc aaactcagat accaaaaccc taaataagat 50340gctagcttat tgatgtgaac aatccaaaag tgcattttaa attagcccag ggttttagag 50400aaagaaaatc tagcaatgtg accaccactt atgttaacaa ttttaagacg aaaatctaca 50460tgatcatatc aatgcatgct acacaaaagc atttgggcaa aaaacccaac acccaccctt 50520gactttttaa actcttagta attaggcata aacagaaatg tacttaatgt gatagaatac 50580actcggtgaa gatacagagg gaatgctccc taaaaccaag cccaagacaa agattcctat 50640ttaacctcaa tagtcaacac tgcagcgaga gtaatctatg gaagacaagg aaaaaagtaa 50700aaacatgaga gacatctgtt gtttaacaga caataagatc acctacttgg aagaggcaaa 50760cgaatcaagc gaaaaactat taaaactgag acaggcttta gtatggaggc tcagcttcag 50820ctgtagtttg ggctaccaaa ttcaactcgc ttgcttggag agttaatcct gcaaagctaa 50880tttctgttga ggtattagga ttgacaagcc tgtgctcctc cctcctcccc catcttcaac 50940actgaaataa cacggtgttt ggaactggat aacagaatct tccaaaaaca aaaattgtcc 51000tgaagggctg acttgtgccc ttactcaaaa aacactttat ctgctgcctg cagctcctac 51060agttgctggt ggataagcct gccaaccagc tcggcgtaat tcttcctgca gagggcaagg 51120aagagcactt tcacaggaaa atttttttcc gaactgtatg ccgcttatta cataaactta 51180cgtgctggca aatggagctc cagcaaaata agatattcag agtcaaactt ccttaggaaa 51240aaaaaaaaaa aaaagcaagc acataacact aatttccttg catgggcact ggggaaggag 51300gtcgttactt ccgcacgccc gcaggtccgc accaccggga aacccacggg caccgcgcgc 51360tgcccccggg ccttccaggt gcactgcgcc gcggcgcccc agctgacccg ggatgcgcag 51420ccctagccct tcccctgtca ccccggccag gaaggggcgg gagcgcggcg gacgccgagg 51480gcgaagggct tctcggtcct ctgcaccacg cagcaccccc aaggcacaac agggagggtg 51540cgggaggctc ccgagaccca ggagccgggg ccgggcgtgc ccgcgcacct gtcccactgc 51600ggcgagggct ggggtcgcct ccagggccgc agctgtcggg agccacctgg ctctcagtcc 51660cgggtccctg cgacaaccct cgggcccgga ggggaggagg cggccacctg ccgctgccac 51720ctgcggcacc ggtcccaccg ctccgggccg ggcaggacag gccaggacgt ccctcctggg 51780ctggggacag gacacgcgac gaggggaccg gggcccccgc ggcgaagacg cagcacgcct 51840tcccagaaag gcagtcccgt gcccccacga cggactgccg gacccccgcg ctcgcccgcc 51900catcccttca gaccacgcgg ctgaggcgca aagagccggc cggcgggcgg gctggcggcg 51960cggctagtac tcaccggccc cgctggctca gcgccgccgc aacccccagc ggccacggct 52020ccgggcgctc actgatgctc aggagaggga cccgcgctcc gccggcgcct ccagccatcg 52080ccgccagggg gcgagcgcga gccgcgcggg gctcgctggg agatgtagta cccggaccgc 52140cgcctgcgcc gtcctccttc agccggcggc cgggggcccc ctctctccca gctctcagtg 52200tctcatctcc ctatctgctc atcctctggt cgcacataat cgatgtttgg gcgtcccaag 52260ccagatgtgg accccatttc cgcactctac actggaggtt ttctaagggt ggtgcccgga 52320ccagcagctt cagcctcatc tgggaacttg agaaaatgca gattctccgt cccacccagc 52380ctattcggtt tttcctgcac taaaaccatg aaggtggggc ccagcagtcc acattctcgc 52440aagcccgtca agtgattctg aggcgccctc cagtttgaga gctatgctca cggcctcacc 52500tccgccccgc aaggagcccg gtcttgcctg tggcgctagc cgcacacgga cacctcatcc 52560tgcggggccc gcccccccgc tgcaccctca ccgcccaacg cctcctccgg gatgcagcgg 52620aggcgcctgg aagtcggcaa ggtcaacatc cccctcagca tcttccctac cctcacggct 52680cctcctccag gggtgcctca tggccagggg ttagaaagag ccactgtgtt tcttgacatg 52740gaagtggcct aagaccttaa tgaaaactgc aggagtggaa tgacagaacc tttggtcata 52800cttgagggcg tgaagctcaa atgaggagga aggaaaggat ccagggagaa taaccaaccc 52860tggcaagttg tggcgcccag gtagaggggc gagcctaggc tagcggttct cgaccagggc 52920cggtgttgcc cctcctcgcc gccccgcgta catttgggga ggtctggaga catttttggt 52980tgtcatgatg cgggagttgc tactgttgcc taagtgggta gacacgaggg tgctcctcaa 53040catcctacct gaaggacagg actgccccac aaggaagaat gatccggccc caaataagaa 53100accctgggct ggtcagcaac aacccctttg ttctgagaag agaggaggaa agaataaaag 53160aagtggggtg aagttttggt ttggtagagg aaacttgaag acattttcac tggaaaggaa 53220gagaggaaga ggagggagat gtctgtaagg acgagcaaac cgggtgacag ctgatttcct 53280catattgaag taatgagtcc tagttataat aaattcctaa taaaaaccca gtttatccct 53340gcaataaact tgtctttttt ttttaaatat actgcttgat tctgtttgct aatattttat 53400ttacaggctt tgcattgata tgcaaaaatg agatgggcaa taattttctt tttgaatgtc 53460taatgttgtt tggtttcaga atcaatgtta tgctcacatc ataaaaaatt tggaaccgag 53520gcaggaggag tgcttgaggc cagaagttcg agaccagtct aggaaacaca gtgagacccc 53580cccatctcta caaaaaaaaa aaaagaaaaa aaaatgggca tgtttgcttt ttccttttac 53640tctgaacaat ttaaggagca ttaaaattat ctattctttg aggtttgatc atttcccagt 53700taaaaatgtt cctcccagcc tgatgctttc tttggggagg gtaaatcttt taaggctaga 53760aaagtttctt ctgtggcaat tttattattt acattttaaa aattattcta gagttaattt 53820tgataaagca tgtatttctt aaaacaaatt atcctttttt tccagatgtt caagtgtatt 53880tgcataaagt tgaggaaagt agtcttttgt gaatctttta acttctccca aatatcttat 53940tttgtgtatt tttgcttctt tattttgtta acttttaaaa gtgtattttt ttttcaaaga 54000atcagctctt aggtttatgt ttttggttat actggagctt ttttcttctt ctttttaaaa 54060tattttttct cctttatttt ttagacgtat tttgatctaa cgtaatcgga agaaggtaaa 54120ttagaatctt ttgttactat tgtgttttta tttctcctta tttctctgaa gtcctgcttt 54180ataaatagta ccatgttatt tgtgcataaa tattcatttg tcttatattc ttgggaattt 54240tcccacttca tcataaaatg accttccttg tctcatttaa tgtgttcaaa ctttgccctg 54300aatttaactt tgtctgatat tttaccatcc tgctgaattt tgtttgttac cccaaacaac 54360ctttgctgtt ttcgtctttt ctgaaccctt tattttaggt aatcccttga attagagcac 54420taagttttgc tttgtgatta aatctgaaaa tctttatctt gccatagatg agttgagccc 54480tattcatgtg acagctatat tatgctgttt catagccctt ttggtccttt tttcactctt 54540gcattgcata ttttgtgttt attgtgtttt gtgtttcttc tgataatttg gaaggtttgt 54600atttttattc agggagttgc cttataatca tactccgcaa tacacatcgt cctcagtttc 54660ttcagactgt ctgttaactc cctattctga ataaaaatga cattgtaatt tccctctttt 54720ttctttaccc cttttcttct cctcacctaa tgtaaatgat tttatccttc tttagtattt 54780gcttttttaa ttaactacat ttataaatat ctttatcact tgatttttaa atcagctttg 54840aatgagatat ttggattcct agatataaaa gatgttaatt ataccatttc cacgttagta 54900ggtttataaa atcatacatt ctgctgtgta accataatcc cacgtttgtt ttagttccac 54960tcctacagtt aaaagattca gaagtattat taacagttat tttgccatag ttttttcccc 55020aacccatttt gtggtaagtt atgatcctgc tttagtttct taagaataat ttatagagca 55080gagtgtggtg gctcacgttt gtaatcccag cactttggga gacaagaggt agaaggatcg 55140cttgaagcca gcagttcaag accaccctga gcaacatagt gagaccttgt ctctacaaaa 55200aattttaaaa tttagccaga cgtagtggcg tgtgcctata gtcccagcta ctcaggaggc 55260tgaggcaaga ggattgctag agcccagaag tttgaggctg cagtgacctc tgattgtgcc 55320actgcacccc agtctgggca agaaagtgag aacctatctc tttaaaataa caataataac 55380ttatgaaaat tatattccct gagtttttca tgtttaaaaa tatttgttgc ctttatcctg 55440taaaagtttg agtataaatt cttgggttat actttattta ttgaagaatg tataagtatt 55500gtcttctaga attgagtgtt gctgtaatga aaccagaagt cagcctggtt tatttttcct 55560cagaaatgag gtaattgccg gccggacacc gtggctcatg cctgtaatcc caacactttg 55620ggaggccgag acaggtggat cacgaggtca ggagattgag accatcctgg ctaacatggt 55680gaaaccccgg ctctactaaa agtacaaaaa gttagctggg catggtggtg gacgcctgta 55740atcccagcta cccgggaggc tgaggcagga gaatggcgtg aacctgggag gaggagcttg 55800cagagagctg agatcgcgcc actgcactcc agcctgggcg acagagtgag actccgtctc 55860aaaaaaacaa aaaaaaaaca aagaagtgaa gtaattgcca tgatgctcca agaattatct 55920ctttgtctat gaaatccaga aatctcactg ttatacattt tggaattatt attctgggcc 55980aatatttcct gggacacaat agattgactc tatagattta attttttttt tttttttgag 56040acagagtctc actgcaatct cagcttactg caacctctgc ctcacgggtt caagcaattc 56100tcctgcctca gcctcccaag tagctgggac tacaggcgcg tggcaccatg cctggctaat 56160ttttgtcttt ttagtagaga cagggtttca ccatgttggc caggctggtc ttgaacgcct 56220aacctcaagt gatccacctg cctcagcctc ccaaagtgct gggattacag gcgtgagcca 56280ccatgcccag cctcaattcc tctttctatc tggtaatttt tctgaagttg aaaacatttg 56340ttctaatacg ttatttcagt gttcttctaa gatgtgtaaa gcaccctatt cccaggtcag 56400cccccatctt gctagtgagc tcggctggtt cttcacaaga gctctggttt tctcctgctt 56460aatctcaagt acctctgtca gcctccacct ggtttatgat ttggagtttt ttggtttttg 56520ttttttgttt ttgacagagt cttactctgt cacccaggct ggagagcagt ggcataatct 56580cagctcactg caacctctgt ctcccaggtt tgagcgattc tcctgcctca gcctactgag 56640tagctgggat tacaggcgcg tgccaccaca cccggctaat ttttgtattt ttagtagaga 56700tggggtttca ccatgttggc cagggtggtc ttgaactcct gacctcaggt aatccacctg 56760cctcagcctc ccaaagtgct gagattacag gcgtgagcca ccgcgcctgg catggtttgg 56820agttttaatc tgtagtttta ataaagatag tgcttatgtt tgtgtttctt atatttcttg 56880gtactcttgg gtaatttgta agatccccat atctacacaa gaagtccatt ttcaattctt 56940ttcttcagac tgtttatttt attttatttt attttatttt tatgtttgag atggagtctc 57000gctgtgtcac ttctggaggc tggagtgcag tggcgcgatc tcaggtcact gcaacctccg 57060tctcccgggt tcaagcaatt ctcctgcctc agcctcccga gtagctggga ttacaggcac 57120ctgccacttt ttaatttttt tagagacaga gtctcgcttt gttgaccagg ctggagtgcg 57180gtggtgcaat catggctgac tataacctcc aaatcctggg ctcaagtgat cctcctgcct 57240cagcctcctg agtagctggg actacaggca catgccacca tgcccagtta attttaattt 57300ttttgtagag acagggtctc catatgttgc ccaggctggc ctcctactcc tggcctcaag 57360taatcctcct acctcagcct cccaaattac taggattata agcatgagcc accatgccca 57420gccttgttct actactttaa tttcatatgt taggtgacca tgtaattgat catccaaacc 57480aggatactgt aagaatgaaa gaggctgaca gtagtatgat gctgggacta gcattgtgca 57540ctgagattat ttctgggaaa gcaggagata cggtcaccct acttatagtg tgcttgtctt 57600tggattgttg aatttggagt ttctatttgc aggcttattt caactgggca gccttgatcc 57660gccctgccca gcaatgctac cgttctctcc accgggtctc tgggacccct tcagtcacta 57720tacttagctc agttccccac cctcccactc cctaaaagcg taaccaggaa tcctgcctca 57780ggtctactgc cgtcttccgt gggctgtttc agttcctatt acccagagtc aaactcccag 57840cattccctac ctgattccag acttggagtc cagagcttta acctcttcag gccaactccc 57900cactttgcat ttctgtccct atatcttagt ccatggagat acatttcatg tctttgagtc 57960tacttacaaa gtaaattttg ctgtttttta attttttttt tgagatggag tcttgccctg 58020tcacccaggc tgtggtgcaa tgacgccatc tcggctcact gcaacctccg cctcctgggt 58080tcaagcgatt catctgcctc agcctcccaa gtagctgtga ttacagacag gcaccaccac 58140gcccagctaa ttttttttat cttttagtag agacagggtt tcaccatgtt ggccaggctg 58200gtcttgaatt cctgacctcg tgatctgccc atctcggcct cccaaagtgc tgagattaca 58260ggcgtgagcc actgtgccca gccaattttg ctttttttat atttcattgc tatatgttta 58320gaggataagt ttacagtgct atatgcattc ccaaatatta gaccaaaaaa atctccaaaa 58380aattagaaag aaaatccaaa aaatctcaaa aaataccaaa aagcaacaat ctcacagacc 58440atactcactg acccccaata aaataaaatt agaaattaac cacaacttaa caaaataaag 58500tactcaagtc agagaggaaa gaggaaataa acatcaaaat tacaaagtct aggcggtggc 58560tcacgcctgt aatcccagca ctttgggagg ccaaggcggg cagatcacaa ggtcaggaat 58620tcgagaccag cctggccaat atggtgaaac cccgtttcca ctaaaaatac aaaaattagc 58680caggcatagt gatgtgtgcc tgtaatccag ccacttggga ggctgaggca ggagaatcac 58740tgaacccagg gagacgaaga ttgcagtgag ccaaaatcgt gccactgcac ttcggcctgg 58800gtgacaaagc gagactccat ctcaaaaaaa aaaaaattac aaactcttta gatagaaatt 58860ttggtgtttt tttttgagac ggagtctcac tctgtcgcag aggctggagt gcagtgggac 58920tatgtcagct caccgcaacc tccatctcct ggattcaagc aattctcctg tctcagcctc 58980ccaagtagct aggattacag gcgcccacca ccagacccag ctagttttta tatttttagt 59040agagatggtg tttcaccatg ttggccaggc tggtctcaaa ctcctgacct caagtgatcc 59100acctgcttca gcctcccaaa gtgctcagat tacaggcgtg agccaccgca ccccacctag 59160atagaaattt caacatgagg ccgggcacaa tggctcacgc ctgtaatctc agcacttcag 59220gaggctgagg cgtgggagga tcacttgggc ccaggagttc aggaccagca tgggtgacag 59280agacagaccc tgtctctatt tatttgaaaa aaaaaaaaaa aaagagagag agaaagaaat 59340ttcaacatga aaagtatctc tcaaaccctt cgagatgttg gcaaaaagcg actcaaagga 59400aaatgtatta ctgtgtgtga atttgcttga aaataagaaa gaggccgggt gtggtggcta 59460acacctgtaa tcccaacact ctgggagtcc gaatcaagtg gatcatgagg tcaggagatc 59520gagaccatcc tggctaacat ggtgaaaccc tgtctctact aaaaatacaa aaaattagct 59580aggcgcggtg gctcatgcct gtaatcccag cactttggga ggctgaggca ggtggatcac 59640ctgaggtcag gggtttgaga ccagcctggc ctacatggtg aaacctcgtc tcttctacaa 59700atacaaaaat tagctgggcg tggtggtggg tgcctgtaat cccagctact cagaggctga 59760ggcaggagaa tcgcttgaac ccgggaggcg gaggttgcgg tgagccgaga tcgcaccact 59820acactccagc ctgggcaaca gcctgggtga cacagtgaga ctccatctca aaaaatacaa 59880aaaattagct gggtgtggtg gcctgcgcct gtagtcccag ctacccggga ggctgaggca 59940ggagaatgga gtgaacctgg gaggaggagc ttgcagtgag ccgagatccc accactgcac 60000tccagcctgg gcgacagagc aagactcttg tctcaaaaaa aagaaaaaaa aaggaaaaaa 60060gaaccctgat aataaagaaa ccaaatgttc aactctcaaa gctcggacac tttaaagaaa 60120taattaataa aggcagaagt taaagggagg atgataaagc aatttttttt gttggttttt 60180ttgagatgga gtcttgctct gtcacccagg ctggagtgca gtgatgcgat cttggctcac 60240tgcaacctct gcctcccggg ttcaagcaat tctcctgcct cagcctcctg agtagctggt 60300actacaggtg cgcgccacct ggcccagcta atttttgtat ttttattaga gacggggttt 60360caccatattt gttaggctgg tctcaaactc ctgatctcag gtaatctgcc cacctcggcc 60420tctcaaagtg ctgggattac aggcaggcgc caccgcgcct ggcctaaagc aaaatattgg 60480ttctgtgcaa aaggtcaata aaaagagcaa acgtttacaa actggagcca gcacccattc 60540agctcagtgt gtctggagaa aaaacaatct cgcttcagaa ttcatgatta cgcagccctt 60600tttgcttcct aaaaatccta ctatgttgct gttgaccatt ctctctcttt ctctctctct 60660tgctttctct ccagaaaagc tattcagaca ttctcctctt tcctcaaacc tccaacactt 60720cctcctccat ccttagcctc agctgctgac ctcacttcta atcattgaga aaccaggaga 60780agcatttaag agtgaacctc cgcctccccg cacgggcaaa accacccacc cacagaattg 60840tgccccaatt ctgcgtcctc tcctctcacc atggatggac ggtccaggct ccgagccaaa 60900gccaggcctc ccctggagct ctggatccac cacctgcagc ttctcaggca gggccccagc 60960agctcccctg ctcccttgta ccatcaatcc ctcccctcac tgggtcactc ccaacaatat 61020atatatttag tgatgtttct cccatgtggt aaaatcactt agcctctctc ctcccccagc 61080tactatccta tttgtttctt tccattctct gcaaaacttc tcaaagcatt gtgtctatgt 61140gctgactcca tttatcttct cccgttctct gctgagtcct tcccacagac tctcacccca 61200gttactccat gaaatgacct ctgcactgcc acatccaatg gtgaatgttc agttcttaat 61260tttattcagt ctttcagcag catttgacct ggccgatcac tccctcttct taaaaatact 61320tttctcagcc aggcgtgatg gctcacacct gtaatcccaa cactttggga ggccaaggcg 61380ggaggatcat gagagcccag gagttcaaga tcagcctggg caacatggca agaccctatc 61440tctacaaaaa ctaaaaagta gccagtgtga tggcatgcac ctgtagtccc atctacttag 61500gaggctgagg cagtaggatg acttgagcct gggaaatcaa ggctgcagtg agccatgatt 61560gcaccactgc actccagcct gagtgacagc gagaccctgt ctcaaaaaga caaaatagga 61620aacttttctc agcatattcc tctgattctc ctgctgcttc tgtctgcaca gattcagtct 61680cctttgccgg ttcttcctca tcctcctgat ctcttgacct tgaagtgccc cagagtacag 61740tctttttttt tttttttgag acgcagtctc gtctgtcacc caagctggag tgcaatggcg 61800aggtctcagc tcatgcaacc tctgcctcct gggttcaagc gattctcctg cctcagcctc 61860ccaagtagcc aggactacag gcacatgcca ccatgcccag caaattgttg tatttttagt 61920agagacaggg ttttactata ttggccacgc tggtctcaaa ctcctgaact cgtgaaccac 61980ccgcctcggc ctcccaaagt gctgagatta caggcatgag ccaccacacc cggcccagag 62040tacagtcttt agacggcctc tctacctata cttgctcccc tcataaactc ctcctgcctc 62100atggctttaa ataccatcgg tagactgatg actcccatat ttctcttttt tttttggaga 62160cggagtctcg ctcagtcccc caggctggag tgcagtggcg cgatctcggc tcactgcaag 62220ctccacctgc caagttcaca ccattctcct acctcagcct ctccagtagc tgggactaca 62280ggcacccgcc accacgcctg gctaattttt ttgtattttt agtagagatg gggtttcacc 62340atgttagcca ggatggtctc gatctcctga cctcgtgatc cgcccatctc ggcctcccaa 62400agtgctggga ttataggtgt gagccaccgt gcccagccga tgactcccat atttctatct 62460cttgctgtgt gggagttctc ctcagaactc catactcata aatccaactc tcataaatag 62520tatctcaaat gggcaatatg ctcaaaagtc aattcctact tttctcccta aacttgcttt 62580cctgcagtct ccaccatctt aatgtccaat ctaacattag gaggcaaaaa ctttgaagtc 62640attcttgact cttctctatt acacacccta tccaatcttt ctgcagatcc agtcgacccc 62700caaatccagt tagctctcat catctcccct gttaccccct ggtccaggcc atcttcctct 62760ctcacctgaa tcactgcagc attctcctca ctggtctctt tggttctgtt ttcactccac 62820cttagcatag tctccacaga gcagtcagag ggatcctttt aaagtgtaat tcccatcctg 62880tccctgctct gctcaaaacc ctgtcgtgat tcccgtttta atctgtcaga ttaaaagcca 62940gagtctttcc agtgacctac atgatctgcc tattatcacc tcccacttct ttccccttgc 63000tcactccact ccagctctgc agctgtcctt tctgtttcct gaacagccca gattttgctt 63060ctttagaacc tttgtatttg ctgtcccctc tgtctggaat gtttttccag gaagtcacct 63120ggctctctcc tgcacttcct tcctgaccac catgtttaaa aatcactcaa acacacttca 63180ggccggacat ggtggctcac gcctgtaatc ccagcacttt gggaggccaa ggtgggtgga 63240tcacctgagg tcaggagttc gagaccagcc tggccaacat ggtgaaactt cgtctctact 63300acaaatacaa atagtagcca ggtgtagtgg cacacacctg taatctcagc tactcaggag 63360gctgaggcag gagaatcgct tgaacccaga aggcagagga ggtgcagtga gccaagatca 63420cgccacaaca ccccagcctg ggtgacagag caagacccca tctcaaaaaa aaaaaaagaa 63480aaaaaaatca cacaaacaca cttctcttca tattcctttt ccaagtttta tttttctcca 63540gaatacttta cattgtttta atggaagttc tccgtttccc cccaactaga atggatactt 63600cctgcaggta ggcactctag tcctcccatc caagtactaa ccaggctcaa ccctgcttag 63660cttctgagag caggggagat caggcctgtt cagggtggta tggcccagga attttgattc 63720tgttttattc attgctgttc tgttgattct cttttgttcc tcctcctagt gctgagaaca 63780ctacttgtac ataataagca ttcaataaat atttgttgaa tgaatgactt gttgaatgaa 63840ttaatctcag aaatgcagga ctggttctac attagaaaat ttttcaaggt cattctctgt 63900tgtcgtaaca cattaagaga ggaaaatttt gtactctaaa tcatttgata aaatacatac 63960tgatttctgt tttcaaaaac tcttagtggc tgggcgaggt ggctcacatc tataatccca 64020gcattttggg aggacgaggt gggcggatca cttgaggtca ggagtttgag accagcctgg 64080ccatcatggt gaaaccctat ctctactgaa aatagaaaaa ttagccgggt gtggtggcgc 64140atgcctgtag tcccagctac ctgggaggct gaggcaggag aatggcttga acccgggagg 64200cggaggttgc agtgagccaa gatcatgcca ttgcactcca gcctgggtaa cagagtgaga 64260ctccatctca aaagaaaact cttagtgagt ttaggaatcc aaggaagacc ctcaaactaa 64320atagataatc tagctaccag aagccttcag taaaccttaa cactccatgg tgaaacatta 64380gaaacattcc tactaaaaga caggctaaga atgcctgcaa tcttcacggc tagtccaaga 64440agtcaaaaag aagaaatgag cgctgattta aaaaaataaa caaacaaaaa actaccgatg 64500cagaggctgg cagcaaggac tgaaggactg tacagtactt gcctggagca ggcggatggc 64560cacacccctg cgaagcctgc tcagctggct gggggacgct ccagtgtgtg agtggcagga 64620tgcagggtac ttcctctgcc agggagttgc actggggaga tcctccccca ctcacacttt 64680ggcagctggg gctttggaat gtgacttagc ttctgtcaaa gggtcaatcc accctttgat 64740atatgatgca aaggcgaaca tatgatgcaa aggtgagaga acagcccaaa ttaggacttt 64800taccacagct gtggaggtgg acagcgacag tggtgggccc tggccagact tttcatgctc 64860aaaggtggtg gttgttcttc ctacttcttg tccctccagg gcttcctttg cctgtgtgct 64920gaacctgctt cttttaattt tttttaactt ttttaaattt ttaattgttt taattaaaac 64980aaattttgaa aactgtctga acctgctttt gaaccctgct atgatttgaa tgtttgtccc 65040ctgccaaact gattttgaaa cttaatctcc aaagtggcaa tattgagatg gggctttaag 65100cagtgactgg atcatgagag ctctgacctc atgagtggat taatggatta atgagttgtc 65160atgggagtgg catcagtggc tttataagag gaagaattaa gacctgagct agcatggtcg 65220ccccttcacc atttgatatc ttacactgcc taggggctct gcagagagtc cccaccaaca 65280agaaggctct caccagatac agctcctcaa ccttgtactt ctcagcctct gtaactgtaa 65340gaaataaatg ccttttcttt atgaattacc cagtttcaga tattctgtta taaacaatag 65400aaaacgaact aaggcaaact ctcatgattc tactgccatg ccattccaat aaactccctt 65460tatgcttaag agagccagag ttggccaggc gtggtgactc acgcctgtaa ttccagcact 65520ttgggaggcc gaggcaggtg gatcacaagg tcaggagatc gagaccatcc tggctaacac 65580ggtgaaaccc cgtctctact aaaaatacaa aaaaattagc tgggcgtggt agtgggtgcc 65640tgtagtccca gctactcggg aggctgaagc aggaggagaa tggcgtggac ccaggaggcg 65700gagcttgcag tgagtcgaga tcgtgccact gcactccagc ctgggtgaca gaatgagact 65760ccgtctcaaa aaaaaagaga gccagagttt atttctgttg cttgcaacca agaaatctgg 65820ctggtgcact gaagtttcca taaataatag caatttaaag actctttcca agccaggcaa 65880tgcctagcct tgtgtagtcc ttgtggtaat acattcattc attcatttgt tcaaccaact 65940gtgctccaga gactaagaat acaaaaatgg gggccgggtg tggtggctca cacctataat 66000cctagcactt tgggaggccg aggcaggtag atcacctgag gtcaggagtt cgagaccaac 66060ctggccaaaa tggtgaaacc cctactctac taaaaataca aaaaattagc tgggggtggt 66120ggcggacacc tgtaatccca gctactcgtg agactgaggc aggagaatca cttgaacccg 66180ggaggcagag gttgcagtga gccgagatcg caccactgca ctccagcctg ggcaacaaga 66240gcgaaactcc acctcgaaaa aaaaaaaaaa aaaaaaagag ggccggggct gggcgcagtg 66300gctcacgcct gtaatcccag cactctggga ggccaaggca ggagaattac gaggtcagca 66360gatcgagacc agcctgacca acatggtgaa accccatctc tactaaaaat acaaaaatta 66420tccgggcgtg gtggcgcaca cctctagtcc cagctacttg ggaggctgag gcaggagaat 66480cgcttgaacc cgggaggcag aggttgcagt gagccgaaat catgccactg cactccagcc 66540tgggtgacag agtgagactc cgtctcaaaa aaaaaataaa aaaaaaaaaa gaattcaaaa 66600attgtagagt tatagtgtgc ttctagttta gttgagagga catctgtcct tcaaggaagg 66660ctagaatcta taccctgagt ccttactgaa atcaatccag cagtcaaaac atgggaccaa 66720cgatcacagc agtaagatag gaagagcacc tttgtacatt tagctcatgt tgagataagc 66780cactgacaga gctgaaggaa gctcacagtt ctgggttcca tcctttggca tttaaaaaga 66840aaagtgctaa gaaaattcgg ttggtcacgg tggctcacgc ctgtaatccc aacactttga 66900gaggccaagg caggcagatc acgaggtcag gagttcgaaa ccagcctggc caacatggtg 66960aaaccccgtc tctactaaaa acagaaaaat tagccgggca tggtggcgca tgcctataat 67020cccagctact caggaggctg aggcaggaga attgcttgaa cccgggaggg ggaggttgca 67080gcgagtgaga gcaggccact gcactccagc ctgggagaca gagcaagact ctgtctcaaa 67140aaaaaaaaag aaaaaaagaa agaaaggaaa aaaagaaaga aaaaaaaaga aaaaagaaaa 67200ttcaggccag gccaggcctg gtggctcaca cctgtaatcc caacactttg ggaggctgaa 67260gcgagacggt gccttagccc aggagtttga gaccagcctg agcaacatag cgagaccctg 67320tctctataaa aaaaaatttt tttttggcca gacgcagtgg ctcacgcctg taatcccagc 67380actttgggag gccgaggcag gtggatcacg aggtcaggag atggagacca tcctggctaa 67440cacggtgaaa ccccatctct actaaaaaat acaaaaaatt aaccgggcgt ggtggcgggc 67500gcctgtagtc ccagctactc gggaggctga ggcaggagaa tggcgtgaac ccgggaggcg 67560gagcttgcag tgagccgaga ttgcgccact gcactccaga ctgggagaga gtgagactcc 67620gtctcaaaaa aaaaaaaaaa aaaaaaaaat taattgtcag gtgtgctggc atgcagctgt 67680agtcctagct actcgggagg ctgaggtaag aagatcgctt gagcccagga gttcaaggct 67740gcagtaatag tgcctctcac tctaccctgg gtgacaatga gaccctctct caaaaagaaa 67800gaaaaaaggg aaagaagaaa agaaagaaag aaagagaaga aaggaaggaa gaaagaaaga 67860aaaagaaaag gaaggaagga agaagaaaaa aaaagaaaga aagaaaagag agagaagttc 67920aaagaccaaa gggtcaggat cccaaaatag tttttatgtt ttatttattt atttacttat 67980ttatttttga gacagtatgg ctctgtcgcc caggctggag tgcagtgatg cgattgcggc 68040tcactgcagc ctccaaactg ggctcaggtg gccctcccac ctcagcctcc cgagtagctg 68100ggaccacagg cgcgtgccac catgcccagc taatttttta attctttgta gagatgaggt 68160ctctatatgc tgcccaggct ggtctcgagc tcctgggctt aagccatcca cccgcctggg 68220cctcccaaag tgctgggatt acagaagtga gccaccgcgc ctaatcgggt ggtttgtttg 68280tttattgacg gggtctcgct gctgcccagg ctggagtgcc agtggctgtt cacaggtgca 68340gtcctggagc attgcatcag ctcttgggct ctagcgatcc tccagagtag ctgcagctgg 68400gattccaggc gcgccaccgc gcggggctca gaatgggttt ttatattgag ggttatgctg 68460ccacctagag gatatatgta gtaccgaact gtgtgcgcag ggaggctgag gttgcagtga 68520gccaagatga tgccagggca ctccagcgtg ggtgacagag caagatttca tctcaaaaaa 68580aaaaaaaaaa aaaaaaaaaa aagaattgaa agtaaggtct tgaagagata tttgtgcctg 68640tatggtcata gcagtattaa ctttgaccca ctagctaaaa cacaaaagca acatgtgtct 68700gtcagcaggt gaacggataa acaaaatgtg gtatatatgt acaattgaat attattcagc 68760ctttaaaaag gaataaaagg ctggatgcgg gggctcacgc ctgtaatcct aacactttgg 68820gagactgagg tgggtggatc acccgaggtt aggagtttga gaacagcctg gccaacatgg 68880tgaaacttca tctctactaa aaatactaaa attagccggg catggtggca cttgtctgta 68940atccaagcta ctggggaggc taaggcagga gaattgcttg aactcaggag ccggaggttg 69000cagtgagcta agatggcacc actgcactcc agcctgggca acagagtgag actccatctc 69060aaaacaaaca aacaaaaaat tattatttcc aaagaaacaa gaccctgggt ccatttccca 69120gcccacacct gatgttgact cacaacacac agcctggttt gctatgagcc tgcttcattt 69180aattgtcacc ttaacttcac atcaccctca agtcctggaa taactctttg ctgacctttg 69240tgtgctgagc catctccatg tcgctcaacg tgcagtccct ctcactgcac tgagtcaata 69300gccagacgtg gtctgactgc agggtcatcc ttggtggctt aggctgactc gggcatagca 69360gggtgctctg agacctcacc gcatataggc tttgccccca ataaactcta tataatattc 69420atattatgtg gtctgggtgt gtgtagcttt gcactgtctt ctcgtgacag tgccctcaac 69480ctctttccca ggatttcctc ctctacctcc tcaagtccca ctgctctgca aagaccaaaa 69540gctgcagagt cccagctccc tcctttacac cccacgacgc agcctcctct ctcagaaccc 69600tttaaacaga gtcttttact gcagatccca agaacagcca cacccctctc tcccacccac 69660tccagacaca cccaggtaat tatagcaccc agggtaacta tgtagatgga gtccctggaa 69720catgtggata gtgccccctg ggagtatgca aaagcaacat tgctggcacc tgcagagaac 69780agggtgacat ccaggaatca gagcatgggc ctctgggagg tagggatgtg gccaggcagg 69840ctgccaaaaa ttggtagagc aaggccacag gatctttctg accttccttc caaacagagg 69900ctcctgtact ggtgatccct gtgttgattg accactccct tcctgggggt cgtggtctct 69960gtcccagttg cccggacttc tgtgagtgtc ctactgaggt ccttttcatg agaagcatgc 70020tgtccttcca cctgctggga gcaagagtga caacttcaat actataatag cagtggcata 70080cagagaagaa gaaagatgaa gtggcaagaa aaacaggctt ccaagcagga gtttttctat 70140aaaaacaaaa acgtttacaa gcaaactttt tataaagggc tagatagtaa atattttagg 70200ctttgagagc cacatagact tgtttgcagg gactcaatgt cgctattgta gtttgaaagc 70260agccatcagg gttatgtaaa tgagtgagtc tgattttgtt tcagcaaaat tttatttacc 70320aaaacagaca atgagtgggc tggatttggc ccatgatcct tagtttgcca actcctgctt 70380tgggctcacc cagatctgat tttgaattct ggctctgcta ctggttagct gcaggagctt 70440ggaaggctct ctgagcctgt ttcctcatct gtaaaattaa agcaataatt tctaacactc 70500aagagtgtta cctcacgcct gtaatcccag cactttggag gctgaggcag gcggatcacc 70560tgaggtcaga agttcaagac cagcgtggcc aacgtggcaa aaccctgtct ctactaaaaa 70620atacaaaaag tagccgggca tggtggcgcg catctgtaat cccagctact tgggaggctg 70680aggcagggat actgctagaa cctgggaggt ggagcgtgca gtgagtggag atcacacctc 70740cacactccag cctggccgac agagcgagac tccatctcaa aaaaaaaaaa aaaaagagtg 70800ttagaaggtt ttgagataat gaataaaaga tgccttgtgt atactaagta ttcaacaact 70860gatagctgca ttggtctaat tataacagtt tagaagcgat tgagtcaaca aatgctggat 70920ttgtcaggga ggacttccta tcaggaggta gatcttgggc tgagtcctga agcaaagata 70980ggcattggat agaggagttg agagaacacc ctaggactgt tattattatt attcgacacg 71040gagtctcttg ctctgtcacc caggctggag tgcagtggcg cgatctcggc tcactgcaac 71100ctctgcctcc caggttcaag cgattctcct gcctcctaag tagctgagac tacaggtgtg 71160tgccaccaca cccggctaat ttttatattt ttagtagaga cagagtttca ccatgttggc 71220catgctggtc tcgaactcct gacttcaggt gatccacccg cctcagcctc ccaaagtgct 71280ggaataacag atgtgagcca ccgcacccag cccagaacca tttttcaatc cttggctctg 71340ccttttatta gctgcaagat ctcaggcaat ttatttaacc tctccaaaga ctcattttct 71400cattcacaaa atgaggcaaa taataatatc tactatccca ggttgtcatg agaattaaat 71460gcaacatgac atttaatgaa atgagaagtc ccttggacat taactggcta aagtatgtgc 71520tcgacaagga tatcatttta ggtggatact tagcatctca gaactgatgc tcacaatgga 71580atatcattga aacgcattaa aattcatttt aaatgattgt aggtagtgag gcaattgaaa 71640gaagaagaca agaggactga ttataatgct tcaggctcac tagtctcctt ttaggaggga 71700aaaacaattt caagttaaat tttaggctct agatttttac ccctgctgct cattagaatc 71760acccagattg atgaaatcag agcccatctg aggctgtgtt tttcatctcc agaatgagag 71820ctgttgtggg gattaagttt ttgaaaaagt acatctaaca ggtgatcgaa aatgatagtg 71880atattattgc agtgatggtc attattgttg ttattattat actgaaagag gcttcagttt 71940tctgatccat aaagtgaggg aattgcatga gaccattgct aagattcctt ctagctctgt 72000ttttttgttt ttgtttttta gacagagtct ctgtcgccca ggctggagtg caatggcatg 72060atcttggctc actgcaacct ccgcctcccg ggttcaaatg atcctcctgt ctcagcctcc 72120gaagtagctg ggactacagg cacacaccac catgcccagc taacttttat atttttaata 72180gaggtggggt ttcaccatat tggtcaggct ggtctcaaac tcctgacctc aggtgatcca 72240cccgcctcgg cctcccaaca tgctgggatt acaggcatga gccactgtgc ccaacccctt 72300ctagctttct tgatcactga ttctagggtt ctctgctgaa atatatttga gacatcctgg 72360ataaaagatc atgcaagagc tcccaatatg gtattaataa ttgattctgg aggcttagct 72420actcctgatg gattagacat gactcaactg cctctcttat gtgtacaaca caacaacaca 72480accaagaaag gttattctgg cattccattt attcagttta tttacagccc ttacttccag 72540cagcacgtta aagatatggc cagggccggg tgcagtggct caagtctgta atcccaggac 72600tttgggaggc caaggtgggc ggatcacaag gtcaggagtt tgagaatctg gcaattcttc 72660agacttagaa gcaaccagct cgataacaca gtcttgtgtg ggctctccct ctgtccctcc 72720ctcgcttccc tcatttctca tccctgcccc tgagactgtg caccttcaca tagccctgcc 72780atgagacctt catctcaggc tttgctttct ggggtaactg aggctaaaca ctgagtggcc 72840ctaaaagagg attgggattt ggaagttaga ttattcacca gagaacagac tttgctgatg 72900atcaggccca ggttgtaatt gttgaaaaaa agagaggatg catagtctta tctcatctcc 72960tagtcaaagt caacaccatg ataaataaga gtcaaatcct gagatgtgaa ttggggacat 73020ttgagtggtt aaccctgaga agcttgcacc ttcagacccc tcaatacccc tgctccccag 73080agaaggctgg acattgacct cagcacaggc aggagccctg caagatgcca tttgtcctac 73140taaagatgga cccctccact ctgtttctag gtaaataacc aaagtcaagt ctccacacag 73200cctgagcaag aaagtcagag cctgctacag gagaaaatac cacactggcc aaaggattca 73260ctagccctgg ccactgtgtg tgggaggaac cagggaatca tgtgtgggag tcaatgttga 73320agctgttgga ctgggggtgg ggtggaatat aagcctggcc ctggggagtt tttcccgttt 73380gagggccttt acccacaact caagatccag tgctatagca ggagatccca gagctagtcc 73440taacagatgg tcaggattga acttggccta gagtaaaatg aggaggatag tgccagaact 73500ttctcaacat actattgagg aagaggtcag aaggcttaag gaggtagtgt aactggaaag 73560gggtcctgat ccagacccca ggagagggtt cttggacctt gcataagaaa gagttcgaga 73620cgagtccacc cagtaaagtg aaagcaattt tattaaagaa gaaacagaaa aatggctact 73680ccatagagca gcgacatggg ctgcttaact gagtgttctt atgattattt cttgattcta 73740tgctaaacaa agggtggatt atttgtgagg tttccaggaa aggggcaggg atttcccaga 73800actgatggat ccccccactt ttagaccata tagagtaact tcctgacgtt gccatggcgt 73860ttgtaaactg tcatggccct ggagggaatg tcttttagca tgttaatgta ttataatgtg 73920tataatgagc agtgaggacg gccagaggtc gctttcatca ccatcttggt tttggtgggt 73980tttggccggc ttctttatca catcctgttt tatgagcagg gtctttatga cctataactt 74040ctcctgccga cctcctatct cctcctgtga ctaagaatgc agcctagcag gtctcagcct 74100cattttacca tggagtcgct ctgattccaa tgcctctgac agcaggaatg ttggaattga 74160attactatgc aagacctgag aagccattgg aggacacagc cttcattagg acactggcat 74220ctgtgacagg ctgggtggtg gtaattgtct gttggccagt gtggactgtg ggagatgcta 74280ctactgtaag atatgacaag gtttctcttc aaacaggctg atccgcttct tattctctaa 74340ttccaagtac caccccccgc ctttcttctc cttttccttc tttctgattt tactacatgc 74400ccaggcatgc tacggcccca gctcacattc ctttccttat ttaaaaatgg actggggctg 74460ggcgcggtgg ctcatgcctg taatcccagc actttgggag gccgaggcgg gcggatcatg 74520aggtcaggag atcgagacca tcctggctaa cacggtgaaa ccccgtctct actaaaaatg 74580caaaaacatt agccaggcgt ggttgcaggt gcctgcagtc ccagcggctc aggaggctga 74640ggcaggagaa tggcgtgaac ctgggaggtg gaggttgcaa tgagccgaga ttgtgccact 74700gcactccagc ctgggtgaca gagcgagact ccgtctcaaa aaaaaaaaaa aaaaaaaaaa 74760tagctgggca tggtggcgcg tgcctgtaat accagctact ctggaggctg aggcaagaga 74820atcgcttgaa cccagtaggc ggaagttgca gtgagccgag atcttgacac tgcactccag 74880cctggtgaca gagtgagact ctgtctcaaa aaaaaaaaaa agaaaaaaaa agacagaaag 74940aaagagcaca gacagagtca caggtatttg cagtaggaag ctgtcaggtt agagtgcacg 75000gaaatagaaa gtatatttta cacttacagc acatcttcgt ttgattagcc acatttaaaa 75060tactgaatag caacgtgtgg ctatttagta ttcactaaaa tcttggacag tgcaagtcta 75120aagaatcctt gatccgtccg gcatggtggc tcacgccttt aatcccagca ctttgggagg 75180ccaaggtgga aggatcactt aaggtcagga gttcgagacc agcctggcca acatggtgaa 75240acctcgtctc tactaataat acaaaaaaaa ttagccgggc atggtggtgc atgcctgtaa 75300tcccaggtac ttgggaggct gaggcaggag aatagcttga atccaggagg cgctgcagtg 75360agccgagatc atgccatgcc actactgcac tccagcctgg gcaacagagt gagactgtct 75420caaaaaaaaa aaaaaaattg ttgggcgtgg tggctcacgc ctgtaatccc agcactttgg 75480gaggctgagg ggggtggatc acctgggttc tggagttcga gaccagcctg gccaacatgg 75540tgaaacccca tctctactaa aaatacaaaa attagctggg cgtggtggtg ggcacctgaa 75600atctcagcta ctcaggaggc tgaggcagga gaatttcttg aacccaggag gcagaggttg 75660cagtgagcca agatcgcgcc tctgcactcc atcctgggtg gcagagcaag actatgtctc 75720aaaaaaaaaa aaaaaaatac ttgattgtct ggacattctg cagaacatca tatggagaca 75780ctatgttgac gacatcatgc tgattgtaag caagaaatgg caagtgttcc agaaacacag 75840tcaagacaca tacatgccag aaggtgagat ataaactcta ctaagattca gtggcctgcc 75900acactggtga catttttaaa cctgctagat gtttgtgtag aaaaggattt aaccttgccc 75960aaagaggggt ctggcctttg tccccagcta ctggacataa tctctttaaa ctcttgaaat 76020atcattcctg atagaagtat ttttgttttg actaggggcc ttgggccagc cagatagcaa 76080caatgtgatc tgggttgggg gctttggatc aggtggcatc agtgtgacct cctgagtggc 76140tagagactag aatcaaccac atgggcagac aacccagctt acatgatgga attccaataa 76200agactttgga cacaagggct tgggtaagct ttcctggttg gcaatgctct atactgggaa 76260acccattctg actccatagg gagaggacaa ctggatattc tcatttggta cctccctggg 76320ctttgcccta tgcatttttc ccttgtctga ttattattat tattatgaga tggaatctcg 76380ctctgtcacc caggctggag tgcagtggaa tgatctcaac tcactgcaac ctctgcctcc 76440ccggttcaag cgattttcct gtctcggcct cccgagtagc tgggactaca gatgcatacc 76500accacacccg gctaattttt ttgtattttt agtagagacg gggtttcacg ttagccagga 76560tggtctcgat ctcctgacct catgttccgc ctgcctcggc ctctcaaagt gctaggaata 76620catgtgtgag ccaccgcgcc cagccccctt ggctgattat taaagtgtat ccttgagctg 76680tagtaaatta taaccgtgaa tataacagct tttagtgagt tttgtgagca cttctagcaa 76740attatcaaac ctaaggatag ccttggggac ccctgaactt gcagttggtg tcagaaataa 76800gggtgctcat gtgtgtacca tgccctctaa ttttgtagtt aattaacttt cacaacttta 76860ttattaccgc ttacactcaa tgtttattca catttatcca cataccactt attctagtgc 76920cttgcatcaa agactttcta tctcatgtac tttattctgc ttgaagtaaa tcctttagga 76980tattcttttt tttttttaaa ctttgcacat acatactttt attttttatt tatttttaat 77040tttgttattt ttgtgggtac gtagtagata tatgtattta tggagtacat gagatgtttt 77100gatacaggca tgcaatgtga aataagcaca tcatggagaa tggggtatcc atcctctcaa 77160gcaatttatc cttcaagtta caaacaatcc aattacactc tttaagttat tttaaaatgt 77220acatttaatt ttgtattgac tagagtcact ctgttgtgct atcaaatata attttttttt 77280tttttgagac agagtctcac tcagtggccc agactgaaag tgcagtggca caagctcggc 77340tcacttcaat ctctgcctcc ctggttcaag cgaatctcct gcctcagcct cccacatagc 77400tgggattaca ggcacacacc accatgccca gctaattttt atattttttt agtagagacg 77460ggttttcgcc atgttggcca ggctggtctt gaactcctgg cctcaaatga tctgaccacc 77520tcagcctccc aaagtgctag gattacaggc atgagccacc acacctggcc aaaatagaat 77580attctttagt gaggtctgct ggtgacaatt tttttctttt ttttgagact gagtctcgct 77640gttgtcagct tgggctggag tgcaatagca cgatctcagc tcactgcaac ctccacctcc 77700cggattccag caattctcct gcctcagcct cccaagtagc tgagagatta caggcaccca 77760ccaccacacg cggctaattt ttgtattttt agtagaaatg ggggttcacc gtgttggcca 77820ggctggtctc gaactcctga cctcaggtga tccacccacc ttggcctccc aaagtgctgg 77880gattacaagc atgagccacc acgcacagcc aattttttcc gtttttgtct gaaatcttat 77940tttgtgtcat ctttgaaata tatttttgat ggatataaaa ttgttggttg atagttatta 78000tcattattat tattattttg agacagggtc tcactctgtt gcctatgctg gggtgtagta 78060atgtgatctc ggttcactgc agacttgacc tcctagggct caggtgatct tcccacctca 78120gcctccctag tagctgggac tacagatgca tgccaccata cccaactaat ttttctattt 78180tttgtagaga tgaggctttg ccacatttcc caggctggtc tctaactcct gagctctagc 78240aatccaccca ccttggcctt acaaagtgct gggccatgac tagccagcag ttacttttta 78300tagcatattg aatatttaat atgaatcttc tggcatccac tgtaactgtt taaaaaatca 78360gctgtttact tggcactctt tttttttttt ttttttttga gacagagtct tgccctgtcg 78420cccaggctgg agtgcagtgg cgtgatcttg gctcactgca agctctgcct cccgggttca 78480cgccattctc ctgcctcagc ctccggagta gctgggacta aaggcgcccg ccaccacgcc 78540cggctgattt ttttgtattt ttcgtagagt tggggtttca ccgtgttagc caggatggtc 78600tcgatctcct gacctcgtga tctgtccgcc tcggcctccc aaagtgctgg gattataggc 78660gtgagccacc gcgcccagcc tctttttttt ttttttttag acggagtctt actctgtcat 78720ctaggctggt gtacagtggc gtgatctcag ctcagtgcaa cctccacctc ctgcctcagc 78780ctgccaaata gctgggatta caggtgcgta ccatcacgcc cggctaattt ttgtattttc 78840agtagagatg gggtttcacc atgttagaca ggctggtctc gaactcctgg cctcaagtga 78900tctgcctgcc ccagcctccc aaagattaca ggcatgagcc accgcacccg gccaagtagc 78960actcctttga aggtaatctg cttcccctac ccctagcaat ttttaacaat ttttcttcat 79020ttttatttcc tgaagttttg ttattaataa tctgtgtgca gatttctttg tatttctttt 79080gtttgcagtt catagtgatt cttgaattag tgtgttggtt tctgttatca ccacaggaaa 79140attgtcagcc gttagctttt caaatatttc cttgctaaat tctctcttct cccctttcgg 79200tacaattgat ttgattaaaa ctaaaaccag ggccgggtgc agtgactcat gcctgtaatc 79260ccaacacttt gagaggctga ggcaggtgga tcacctaagc tcaggagttc aagaccagcc 79320tggccaatat ggtgaaaccc cgtctctact aaaaatacaa aaattaccag gcatggtggc 79380acacatttgt agtcaggagg ctgaggcagg agaattgctt gaatccagga ggtggaggtt 79440gcagtgagct gagatcccac cactgcagtc tggcctgggc gacagagtga gatgagaatc 79500tgtctcgaaa aaaaaagtta tgaatgtttg ataaactata tttgttagaa tgtttgttgt 79560agaatactat tcattgattt ttaaacaatg ttagattaaa ccattcactg gatttgtgat 79620aattaactta ctgattttac ctcactgatt tgttgtaatt aatacaactg gtataaaaag 79680actgtgacga ggccgggcat ggtggctccc gcctataatc ccagcacttt gggaggctga 79740ggcaggcgga tcacctgagg tcaggagttc aagaccagcc tgaccaacat ggtgaaaccc 79800catctttact aaaaatacaa aattagccgg tcgtggtggt gcatgcctgt aatcccagct 79860cttcgggagg ctgtggcagg agaatcactt gaacccggga ggtggaggtt gcagtgagcc 79920gatatcgcgc cattgcactc cagcctgggc aacaagagcg aaactccgtc taaaaaaaaa 79980aaagaaaaaa aacacataaa acaaaacaac actgtgacgg ttcccaaaaa ttaggagcat 80040aattaaagga actcctgata aaaattaatt ttatcttaca tgtaaactaa aatgacttta 80100tgaagttaat tcagaaatac aatgcagggt attagtttgc cacagctgcg tattcagcct 80160aatgtaatat tcttgttatt tttaaattct tcttttaact ttactcatat gtggatcatc 80220aaatttcaaa agattaaatg acaatactct tagcagcaag cttccctaag catataaaca 80280ttttaatggg tgatgattca gaaggtaccc gaagaatatg tactgccaga tatcattcac 80340ccccatatac ctgcccgaca gacatcccat tttgggaccc tggataaatg tgtgggtgga 80400gagaaagata ggagaaagtg gtataagcaa atggctttgg agtctgattg acagcgattg 80460aaatcctgtc tctacctctt aacagcctca tgatcctaca taagttaccc cgatcctcag 80520ggccacatct gtaaattggg ggttgcgatg gcagccatct cacagggtct cttttcgggg 80580aagggcagga attatggatt aagtgagcta gtaattgtaa agcacttaat acaaggaggg 80640cgcataataa gtacttcata aataatgacg gccattatca tgactgaggt gtatgcagct 80700gtcggggatt acggcgactt cagaatttct ggtgggcagg gctcaaaggc agcaaatcac 80760actggaagtc gaggtgaggc actgcttctg cacagactgc ttagctggag agaatgagga 80820aggcttagag gagatttaga ggaacttaga gtcctccgcc tccaactctg tgggatctgc 80880tcccgtgcca gagacattca ggggatttct cgcactctcc cctcccctac gtccctcccg 80940ccccatccaa ctaaccacac aacacataca aaatagcccc tgcgaggttc tgcacgctgg 81000aagggaacag gagaagggcg ctgcgctttc ttgctgatgc cctgtacttg ggcccctggt 81060agacacagcc acttgtcccc tcagcctgca gagaaatccc acgtagaccg cgcccgggtc 81120cttggcttca gccaatctcc ctttggtggg ggtgggatgc acgatccaag gttttattgg 81180ctacagacag cggggtgtgg tccgccaaga acacagattg gctcccgagg gcatctcgga 81240tccctggtgg ggcgccgctc agcctcccgg tgcaggcccg gccgaggcca ggaggaagcg 81300gccagaccgc gtccattcgg cgccagctca ctccggacgt ccggagcctc tgccagcgct 81360gcttccgtcc agtgcgcctg gacgcgctgt ccttaactgg agaaaggctt caccttgaaa 81420tccaggcttc atccctagtt agcgtgtgac cttgagcagt tgactttatt tttcagtgcc 81480tagttttcca gataccagga ctgactccaa ggactattac tcatctggag ggtttagcac 81540agtaccgtcg catagtaaat ttccatgtca gttttggtta cctttcatgc acttgcaaac 81600atgccatgct ctgaaacgaa ataggcacat cttttttttt ttttttttta aggagtcttc 81660ctctcgccca ggctggagtg cagtggcgcg atcttggctc actgcaacct ccacctcccg 81720tgttcgagat tctcctgcct cagcctcctg attagctggg actacaggca tgccacgacg 81780cccagttaat ttttgtattt ttagtagaga cggggtttcg ccatcttggc caggctggtc 81840taactcctga cctcaggtga tctgactgcc tcagcctctc aaagtgttgg gattacaggc 81900ataagccact gcatctggcc agaaatgaaa taagtaaatc ttttaacctg ctctaacaat 81960atagtgaaaa gaccatatta ttattagagc aggttaaggg atttgcctat ttcgggttct 82020agttatagtc ttaaacttgg acattcttgt agaaagtaaa aagtttcctc ttcaaagttc 82080cccttcttgt taaagaatac atcataagtg ttagaagtaa tagtttattt taaagactaa 82140ctttcttcaa gcctccttgc tttgtgctaa taactctttg ttaagcccta tcctatgtaa 82200ctgttggaca tgctcacagg cacgttccag ttcacagcct atgccccttc cttatttgga 82260aatgttattg cttccttaaa cctttcggta agcaacttcc tctccttctt cgttcttcct 82320tgcacttacc tatttagaaa gttttaggct attagcaaat cggctatcag tttaagagtg 82380tgaggtcccg ctccagccaa tggatgcagg acatagcagt gaggacgacc caaatgcgta 82440agggataaat atgtttgctt ttcctttgtt caggtgtgct ctcgacatcg ttccatctgc 82500gattgagcac cctttctgca gaaagtaaag attgccttgc tggagatctt ttgtctccgt 82560gctgactttt cttcgtggca ccgattatct atttctaaca attttggtat ttctaacatt 82620ctgaacaatc ttgggctagt tgtctcttct gggcctgttt ccccatccgt cacatgataa 82680acttcattgg tttaaaaacc ccagcgaaca tttattgagt tactattacc ttcctgccct 82740ccccaacccc aaccccaggg agcagttaca acctcagccg ctgagcgcac tcgccgggtg 82800ttaagaagca ccaaagacag ggaggcttga ttgattttgc tttgggagta gagggtcaga 82860agattcacag gaaaatggca tttgagcaag gatgattcac tggagctagc ttttaaatac 82920tggcgaggct tttatgttgc agtcccttac aaagttgagc attcgcaggg actgcactcc 82980gaaataagcc cgcttcccct tttcattcgc taatgatcca gggagctgct ggttccgcat 83040gcggcaggtt gtgccttttc ctaatcaggg ttctgcatcg cctcgaaccc gcaggccgtg 83100gcgggttctc ctgaggaagc agggactggg gtgcagggtg aagctgctcg tgccggccag 83160cgcctgtgag caaaactcaa acggaggagc aggaggggtc gagctggagc gtggcagggt 83220tgaccctgcc ttttagaagg gcacaatttg aagggtaccc aggggccgga agccggggac 83280ctaaggcccg ccccgttcca gctgctggga gggctcccgc cccagggagt tagttttgca 83340gagactgggt ctgcagcgct ccaccggggg ccggcgacag acgccacaaa acagctgcag 83400gaacggtggc tcgctccagg cacccagggc ccgggaaaga ggcgcgggta gcacgcgcgg 83460gtcacgtggg cgatgcgggc gtgcgcccct gcacccgcgg gagggggatg gggaaaaggg 83520gcggggccgg cgcttgacct cccgtgaagc ctagcgcggg gaaggaccgg aactccgggc 83580gggcggcttg ttgataatat ggcggctgga gctgcctggg catcccgagg aggcggtggg 83640gcccactccc ggaagaaggg tcccttttcg cgctagtgca gcggcccctc tggacccgga 83700agtccgggcc ggttgctgaa tgaggggagc cgggccctcc ccgcgccagt ccccccgcac 83760cctccgtccc gacccgggcc ccgccatgtc cttcttccgg cggaaaggta gctgaggggg 83820cgccggcggg gagtcaggcc gggcctcagg ggcggcggtg gggcaggtgg gcctgcgagg 83880gctttcccca aggcggcagc aaggccttca gcgagcctcg acctcggcgc agatgccccc 83940tgagtgcctt gctctgctcc gggactcttc tgggagggag aaggtggcct tcttgcgcga 84000ggtcagagga gtattgtcgc gctggttcag aagcgattgc taaagcccat agaagttcct 84060gcctgtttgg ttaagaacag ttcttaggtg ggggttagtt tttttgtgtt tctttgagga 84120ccgtggatca agatcaagga aatctcttta gaaccttatt atggaagtct gaagtttcca 84180aatgttgagg gttttatgtc taaaagcaac acgtgaaaaa attgttttct tcacccagtg 84240ctgtcttcca atttcctctt tggggggagg ggtagttact gctgttacta aaataaaatt 84300acttattgct aaagttcccc aacaggaaga ccactacttt tgatgacttt ggcaagtttg 84360ctaactactg gaaccctaac ttacaaacga actacttaca tttttgattt ccagttgtat 84420tacctgccca atgtttacgt agaaacagct taattttgat tctgggtaac gttgttgcac 84480ttcattaaaa atacatatcc gaagtgagca agtatgggtc tgtggacagc agtgattttt 84540cctgtcaatt cctgttgctt cagataaaat gtaccagaca gaggccgggc gcggtggctc 84600acgcctgtaa tcccagcact ttgggaggct tggcgggtgg atcacctgag atcgggagtt 84660caagaccagc ctgaccaaca tggagaaacc ccgtgtctac taaaaataca aaattagcca 84720gggtggtggc gcatgcctgt aatgccagct acttgggagg ctgaagcagg agaatcgctt 84780gaacctggga ggcggaggtt gcggtgagcc gagatagcac cattgcactc cagcctgggc 84840aaaaagagcg aaactccgtc tcaaaaaaaa agtaccagac agaaatgggt tttgttttct 84900ttttttgttt tgagacggag tttcgctctt gttgcccagg ctcgagtgca atggcgcgat 84960ctcagtctcg gctcactgca acctctgtct cccaggttta atcgattctc ctgcctcagc 85020ctcccaagta gctgggatta cccatgcccc accatgcccg gctaattttt gtatttttag 85080tagaaacggg gcttcaccat gttaggctgg tcttgaaccc ctgacctcaa gtgggcctcc 85140cacctcggcc tcccaaagtg ccaggattac aggcatgagc caccgcggcc agccagaaat 85200gggttttgga aaaagcacta aacaaaatcg aacttggttt catatgacag ctctgctgct 85260aactgtaaca ggggcagacc agttaaccta cttttctgtc ttctgtcagc tgagaattag 85320atgattccca aaggcccatt gaactctgaa tgactttaaa tacttcttct taagtgggta 85380cacggttttg gtaactgatg ccaggtgatg aatgcatgaa agtgcttaat gaatgaaacc 85440ggtaaaatag taggaggaag ctttattggt aaggcagggg tatacctaat agctctctaa 85500tttattggta ttgaagtggt taacttttgt ttttttaagg ggggaaaaca ttctaagaat 85560aatgaggcaa actgcatatt gcacaagaga ctgttgtctc tattcaacaa ataccttttg 85620agtgtccaga gtctgccagg tgctgtgcta ggccctcacg attgagtagt gaaccagaga 85680atgtccctgc acccatggag cttattgtct actggggtag acagataata aataagcaaa 85740caaatcttct ctcttctccc tttcgctcca tgtaagtgtg tgtgtatagg tgtatactta 85800caagttgagt aaagtgttat gaaagattaa gaggagaaat gcattttggt tagatgttag 85860aggactcagc aggtgacctt gaaacttaga gctgaaggat cagtaggagg taactagaga 85920ggccagggaa tcgcatgttc aaaggccagg aggcaagaaa gagcatggtg cccttcaaga 85980gaggaaagaa ggctactgtg actggagcat agatgtaggc aagtgttggg tgattgagag 86040ctctacgggc catggttagg ttttattcct aatgccgaga tgccaaacat ggtggttcat 86100atctgtaatc ccagtatttt aggaggccga ggcaggaata tagcttgaac ccaggagttc 86160aagaccagcc tgagcaacat gagacctgta caaaacattt aaaaaattgc tgggtatgat 86220ggtgcacacc tgtggtccca gctactcagg aggctgaggc agaaggatca cttgagccta 86280ggaggtggag gctacaatga gccatatttg agtcactaca ctccagcctg gatgacaaag 86340tgagaccatg tgtcaaacaa aatacagaaa gaatattaat ttaaaatttt gaaagaggag 86400tgatctgaac ttatatctta aaaagatcat tctagggcat ggtggctcat gcctgtaatc 86460aagggctttg ggaggctgag acaggaggat cacctgaggc cagttcgaga tcaacctgta 86520cagcatagag agactccatc tctacaaaaa gaaaaaataa atagctgggt gttgtgagtt 86580attcaggagg ctgaagcaga aagatcactt gagcccagga gtttgaggct gcagtaagct 86640atgatcccac cactgcaaca cagtgagatc ttgtctcaaa aaaaaaaaaa aatcattcta 86700ggtgcttttt ggaggctgga tgtggtaaga gtagaagctg gagatggtcc tgttagggat 86760tcgattcaga ctttaaatac catcaatgca ttgagtccca aatttacatc actacgttgg 86820atccttgccc ctgaatccag actggtatat ccaactttag gttcagtttg tatctctacc 86880tgaccaatat agaggtgtcc agtcttttgg cttccctagg ccacattgga agaagaattg 86940tcttgagcca cacatagagt acactaacgc taacaatagc agatgagcta aaaaaaaatc 87000gcaaaactta taatgtttta agaaagttta cgaatttgtg ttgggcacat tcagagccat 87060cctgggccgc gggatggaca agcttaatcc agtagatacc ttcaacttac aatatctaaa 87120attttatgcc agatttagtc attttaaacc tgctcatcag tttttctcaa gaagtagtat 87180tttggctttt tttcttttct tttttttgag atggagtttc gctcttatcg ttcaagctgg 87240agtgcagtgg cggatcttgg ctcactgcaa cctccgcctc ctgggttcaa gtgattctcc 87300tgcctcagcc tcgcaagtag ctggaattac aggcatgcgc caccatgacc agctaatttt 87360tggagacagg gtttcaccat gttggtcagg ctggttttgt actcctgacc tcaggtgatc 87420tgcctgcctc ggcctcccaa aggctgggat tacaggcatg agccaccgct cccggctgca 87480tttttggatt tttagttgct cagcccaaaa ctttagtaca tctttgaacc tcttctttcc 87540tcctactcta tatctgatcc atcagcaaat ctgttaggtc tacctcacac atatcgaaat 87600cctaccacgt ctcaccatct gtgacaatta acaccctggt ctaggcagtc atctctgtta 87660agattgagtg gttaaggatg tcctctaagg agatgacatt caaatcttag cttaaatgtc 87720aagagggagc tggttttata aagattgagg aggcagcatt attttgccat aggcttccat 87780ttggtttcca ttccattctt gatacttatg gtatatattc aaaacaaatg cacagaaaca 87840gacccaggta tattgggaat ttcggatata gagttcctag ttgggaaaag atagactgat 87900ctgtaaatga tgctagttat ccatcatctg gcaaaaaata atttcctgcc tcctctcata 87960tatctcagat caacagactt tttctgttaa gggccaaatc ataaatattt taggctttcc 88020agaccatatg gtttctgtca cactctcctt tatccttgaa gccatagaca atatgtaaac 88080aaatgggcat ggctgtgcta cgataaaact ttacttacaa aaactggtag tgggccagtt 88140taggcatggc cagcactttg ggaggctaag gcagatggat cacttggggt caggagtttg 88200agaccagcct ggccaacatg gtgaaaccct gtctctacta aaaatacaaa aaatagctgg 88260gcatggtggt gggtgtctat aattccagct actctggagg ctaagacaca agaatcactt 88320gaacccagga ggcagaggtt gcagtgagct gagatagcac cactgcactc cagccagggt 88380gacggagtct taaagcaaaa caaaacaaaa ggtagtgggt tgtatttggc ccatgggctg 88440tagtttgcca atccctgatg cagaaacaaa ttccaggtaa ataagagcct ggaatgttaa 88500aaaaacaaaa cttgaagtca tgtagaagaa caggtagggg gaacaatcct gatctcagga 88560taggaaggga tattgcttaa aataagacac aggaaaatat aatccatgtt gtgtaaattt 88620gactacgtta aaacttaaaa ctttcgccaa gcgcggtggc tcacgcctgt aataccagta 88680ctttgggagg ccgaggtgag cagatcacca ggtcaggaga ttgagaccat cctggctaac 88740acggtgaaac cccgtctcta ctaaaaatac aaaacattag ccgggcgtgg tggcgggcgc 88800ctgtagtccc agctacttgg gaggctgagg caggagaatg gcctgaaccc gggaggcgaa 88860gcttgcagtg agctgagatc gcgccactgc actccagcct gggcgacaga gtgagattcc 88920gtctcaaaaa aacaaaacaa aacaaagcaa aaaacctaaa actttcatac aataaagtat 88980acctaagata cttctagaag agaagattta catccaggac gtgtatggaa tttctgcaag 89040taataagtaa aagacaaggg acatgaagag gcagttcaca aaagaggaag ccaaaatgac 89100caataaacat gaaaggatgt ttaacctcaa aggaaacaag gaaatgaatt aaaaacatca 89160aatgccattt caaaactagt aagttggcaa aattaaaaat accaaggatg agaatatgaa 89220gcatggctat atgagtgcat ggaatggtac agtcactttc attaaaaatg cacataattt 89280gttttttatt tatttttttg agacagtcta tgtcgcccag gctagaatgc agtggcatga 89340tctcggctca ccacaatctc tgcctcctgg gttcaagcaa ttctcctgcc tcagcctcct 89400gagtagctgg gattacaggc acatgccaca acgcccggtt aagttttgta tttttagtag 89460agacagggtt ttgccatgtt ggccaggctg gtctcgaact cctgacctca ggtgagctgc 89520ttcccaaagt gctgggatta gaggcgtgag ccaatgctcc tggctgaaaa aaatgcacat 89580aatttgttac ctagcaattc catgtctaga ggcttatcct agagaaattc ttgcttatat 89640gcataggaag acgtgtacta gaatgttcac tagttgaatg tttaagtgaa aattaggaaa 89700taaagtaaat gttcattaac aggaaaatga gtaaaggtat atttataaaa caattaagta 89760gctaaaatga ataaactaga gctgcgtgaa tgaactagaa ctggttcaat agtcatgtca 89820gattattgaa tgaatacagg tcagatatgt atagagtgtc atttgtgtaa ttaatttttt 89880tttttttttt gagatggagt ctcactctgt tgcccaggct ggagtgcagt ggcgtgatct 89940cagctcactg caacctccac ctcctgggtt aaagtgattc tcctgcctca gcctcccgag 90000tagttgggat tacaggcatg caccaccatg cccagctcat tttcctattt ttagtggcca 90060cagggtttca ccatgttggc caggctggtc ttgaactcct gacctcaagt gttccaccca 90120acttggcctc ccaaagtgct aggattacag gcgtgagcca ccgtgctcag ccatttgcgt 90180gatttttaaa gatgtgcaga ataatgccat taaaaaaaat acacatacat gtatatatat 90240acacgtttgg ctgggtgtgg tggctcacac ctgtaatccc agcactttgg gaggctgagg 90300caggaggatc acttgagccc aggtgtacaa gactagcctg ggcgagatag caagacccca 90360tctcaacaac agaaaggata attaggtatg gtggcatgag aggatcactt gagcccagga 90420gttcgagtgt tatcaggcca ctgcactcta gcctggacaa caaagcaaga ccgtgtctca 90480aaaaaataaa aataaaaagt atttgtatgt ggtcatagtc aaaaaacgta catggaagga 90540aaatgtcttt atttatttat ttattttttt ttttttaaga cagagtcttg ctctgtcacc 90600caggctgggg tacagtggtg taatctcagc tcaccgcaat ctcggcctcc cgggttcaag 90660cgattcttct gcctcagcct tctaagtagc tgggactaca ggtacccgcc accacaccct 90720gctaattctt gtgttttcag tagagacagg gtttcaccat gttggcaagg ctggtctcga 90780actcctgacc ttaagtgagc cacccgcctt ggcctcccaa agtcctggga ttacaggtgt 90840gagccactgc gcttggccag gaaatatcta atttagtaag tatttatatc tgggaaagga 90900agggtcaggt ggtgattcat aggaactcta aagtctatgt ataatactta gggggacaga 90960aggaaataaa gcaaaatgct gatatttgat tgttgagttg tgtatatgtt agaagtataa 91020cataggagat ctgattgata gtaggagaat gtttttaggt ggtaaaagtg gaaccgtggt 91080ggtttgtttt ggcagtagaa tcagttggtc atagtttgta tgtggaaggt aataaacaga 91140ccatgttaag gatgacttcc ggaattttgg tctgagtagt gggtggatga cagtgtcatt 91200catgagggaa gatgaagact gaggtaggaa caggtttggg agaagatgac atgttccctt 91260ttagacaagt ggaattatgg aagatggcag gtaggtggtt agctatatga atttgagata 91320aaagatttag gatggagata taaatttagg agtaacagcg tatctatggt attgtaagcc 91380ttaagaatgg gtaggatcag ccaggaaata cagatgtata tgcagaagag aggagtcaag 91440gaagccaaga caagttaatg tttaaagtga gtgatgtagt ccatgggcag atgctgctga 91500gagggctgca aacaccagtg accctacaac atttttaaat gtcgtcttcc tgacagcagt 91560gatcagtacc tgcaacgatc ttatttattt ttttcatgtt agtctccaca cacttgaatg 91620tagacttttt gaaggcaaaa tcattgcctt ttctgagctg ggagcatgtc tggcacatac 91680caagcactca acagttgatg tattgacttc atccagatac tctgagggcg agttatttcc 91740tgctactagc ctttcacctt tcaatgttta agagcacaaa tacagagatg ggcacgtttt 91800ggcatttctt attttgataa ccttttcctg gtaagatttt ttaatgttga aaaaaaaaaa 91860caagaaaaga gggttaaaaa tagtcttatg tcagatcctg tgatagaatt cacacttggc 91920ttaagctgct gggcaccttc ctatcttgga tgtcatatta gcttatctac agcagaattt 91980ttactgtttt atgtagtaag gaagcaatta tatgattatt ttacagacaa attattcttt 92040atcttttatt tttttagacg gagtctctct ttgtctccca ggctggagta cagtgtcgcg 92100atctcggctc actgcaacct ccgcctcctg ggttcaagca attctctgcc tcagcctccc 92160aagtagctgg gcttacaggt gtccgccacc acacccagct cattgttttg tatttttagt 92220agagatgggg tttcaccatg ttggccaggc tggtcttgag ctactgacct caggtgatcc 92280acccgccttg gcatcccaaa gtgctggaat tacaggcgtg agccaccgtg cctggcccag 92340acaaattatt atactctgag tgttagaggc ttaggatgtt ttcacttgat gctatgggag 92400gaataagtaa taagatatga tacacaacca aagacctttc ttcactatgc ttctagtagc 92460tagtactatg gatgacacat ggtaataata ttggttagca tttgtcctca atttactgtg 92520ctagttactc ttctaagccc cttacaggta tatatttttt ttcatcaata atcctctaag 92580gtagttttta ttattgacct aattttataa atcaagaaaa ttaagaccca gagaagtaag 92640taacttgtcc aagatcacat ggcttataag tggtagagcc agaatttgac cccagatgtt 92700gtgactacat tgtctctcca taagcaggtt caactctttt gactggatgc tgttccaagg 92760tcacttcctt agagaagcct ttgctgacaa ctaccctcct gtgccctcct ccaaggctgt 92820ccattgttct agaactttga atactcatct tagaataaag ctggtctaat ttttacagtg 92880ttatagaatg gatctctgac tgcaaaagtt ggtcataatt atctttttat gttctagtga 92940aaggcaaaga acaagagaag acctcagatg tgaagtccat taaaggtaag ttctgccctt 93000ggcagtccac tgcattaaaa agtgatgtgc tttgcatttg tgagttcttt aatcctgtta 93060tactctctct tttggcatta atcatttctg ccttatttta taattactta tgattttgat 93120ttatttccct ctttaacctg tataatgctt taacatctag catataataa gtaggctttt 93180tttttttttt tttttttgga gacggagtct tgctctgtta cccaggctgg agtgcagtgg 93240cgcgatcttg gctcactgca agctctgtct cccgggttca caccattctc ctgcctcagc 93300ctccccagca gctgggacta caggtgcacg gcgccacgcc tggctaattt tttgtatttt 93360ttagtagaga cagagtttca ccatgttagc cagtatggtc tcgatctcct gaccttgtga 93420tccgcccgcc tcggcctccc aaagtgctgg gattacaagc gtgagccacc gcacccggcc 93480gtaagtaggc tttttttacc ttaattttat ttttttgaga tggagtcttg ctcttatccc 93540caggctggag tgcagtggtg ccatctcggc tcactgcagc atccacctcc cgggttcaag 93600cgattctcct gcctcagcct cccgagtagc tgggattaca ggtggccgcc accatgccca 93660gctaattttt gtatttttag tagagacagg gtttcaccgt gttggccagg ccagtctcaa 93720actcctgacc tcaagtgatc cactcgcctt ggcctcccaa agtcctggga ttacaggcgt 93780gagccaccat gcctggccat aagtaggctt ttactgagcc ttgtgtgtat tggctatcct 93840agtgattaca gtgaaccagt gcccttctta ttaatcacac atttaattgt tccctaaaag 93900tgattagttc actttattta tttagtaaga caaaaaatga agaatactct taactgagca 93960gtctgttaac tgtaggaaag cactgacact tataaggctt agttttctgt catttatcca 94020gaagtatggt tgattacagt ttttactttt ttatttgaat gaacaacctt aatttaaaat 94080atattttgtt tattttttgt tgggatcgat acattgtcct tgtttataga ttagagcatg 94140ctttttaaag atgctgtatt actcactgat tttatttgtc cagtgtacag agattgaagt 94200gggaaaatta taatggaaat tgtttccata gtcattacat attaatttca tcaatttatt 94260tccataaaat ctgtagattg ctacttattt agatttttcc ttcaaatgtt tttatgttgt 94320attgcttgca ctgagtattt attctatatg ctcaatttgc tggagaagaa gactaattat 94380aacttaggca agttgtaaaa ttagggaaaa aagtaaggta ccttacagcc tagtttactt 94440atttcttatg taaagccagt tagattccac attagttcaa actgccttct ttgagcaaaa 94500cttgattggc agtgataaag gcttaaagcc cttctcaagc agagacctgt aaagactaga 94560tctgactgta gtagaaggaa ggaacttaga tgtttcaggc agtgagaaca ccagtcttcc 94620actctaaact ttgccactaa cagtatgacc ttgggaagtt gtaactttct tcagattctt 94680catttgttga atggggggat tggcctagct aatttctaaa tctctactgg gctaaaaaat 94740tctgtgctta tactctgatt atgaagtaca taatctgtgc ttaacattca ctgacttatc 94800cttaggataa tacagaagca gtacaagaaa cagcccctca agatgtttgc agtctggtta 94860gaaagacaaa cttatacaca gaacagtagc aaatagacca aaataataat agctgccatt 94920tatagaacac ttcttctgtt ctgggcatta gacaaaaact gactataacg gtgaacaaaa 94980aagacttagg tcctgccctc attgaactta cagattagta ggggagagga acattaatca 95040agtaattcca cagatggctt agcctagatt ggtagtgatg gaagtaaaga gatgtgaacg 95100gacttgaaaa aaaattcgga ggcaaaatgg atagaagttt attattgatt aaatatgagg 95160tgtgagagag agggatattt aagattgata cctaccttct ggcttgccta acagaaccaa 95220aacaggaaat tatatgttca gttttgttat gttgggtggg aggtgctttt gagtcattca 95280tttatatatg ttatatatgt tattttatat gcatagtaat tttaaggtct gagttttaaa 95340ccaaaggtta gagagtgatt ttttagagtc tagcaaacct aagttgaaat cctgcctgtt 95400gaaatggctg tttactagct cattaaccta gggcaaagta ttcaacttgt tttcattttt 95460gtcttcatct ctaaaatgag gaaaatatgg tcttacaaga ttgtcctgag agatagatga 95520aataatatcc aaaaaaaaaa aaggtacata gagaaactcg tatagtgcct ggtatatagt 95580aggtcctcca ttggtagcta tcattatcta gttttaacat agccttcagt ttgttgaatt 95640agtcaaactg agtgaagcac tgcaaggaat tcagaggaat ttgagatcaa caaatgattt 95700ctgaagttta gggaagactt catggcaatg acacttacct tgtataaaag ttgaagaata 95760agaaagattt gaatgagaga ttctttctct tctccctacc agcccagctt cttatttgag 95820gatatattgg gcaaaggggc cttcagacaa gtagagggag atttttacag aaagattgag 95880atgaaggtat agaaggctgt aaagaccaga aaagagaatt gagacagagg aagcaggaag 95940ccactgtagg tttttgagca agatattgat gctgtaagta tggtgtttat gaaaggttag 96000tctggaagag atttgcagga tggagacccc ggaagttttt ttgttataat acagaaagac 96060ttgcactgag ggtgaggtgt taaaaataaa caggtaagta aatgtttaaa catcttgaag 96120gaaaagtcaa caaatcttgg caagtaaaca gataacagtg aaaaagaatg ggaccaagat 96180tttgagtttt ggagactggt ggattgaaca gacagggaaa ttgagaggag aatcagatga 96240tgatgtttta agttgatatt tagacagatt gtgcttgaga tggtaaagtc aatgtgggtg 96300ggaatgctta gtagcgagta atcagtgata caagaccaaa gcccaggtca aagacaagtc 96360acagatacag atcagggctt tttcatctgc tccacagagg tgtaccctag gagctgttgc 96420aaacagtcca tgtggagggt gtgagtaaga tgtttccctt gaatttgcca gaattacttt 96480tttgttgttg ttgttgtttt ttctgagaca gattctcgct ctgttgccca ggctggaggg 96540cagtggcgag atcgcgcagc tcactgcaac ctctgcctct cgggttcgag tgattctcct 96600gcctcagcct cccaagtagc tgggattaca ggcttgtgcc accaagccca gctaatttct 96660tttgtatttt tagtagagat ggggtttcac catgttggcc agactggtct cgaactcctg 96720gcctcgtgat ctgcctgcct cagcctccaa aagttctggg attacaggcg tgaaccactg 96780cacccggtcc cttgttaagt ttattttggt gggaagcaaa ggaggtttca gcttttaaaa 96840agtttgaaaa ttattgctct ggtaataatt aaagatttga gagtaaatat gctttctagc 96900agaaagaata aaagaagaac agatagcctc aagaagggga gccaaagaag caggctatat 96960ctgacacact gggtgttgat aaatgggtat taaaagaatg agagcaatga gcagatagaa 97020gaggaaatta ggagagtata ataccatgga gaccaagaaa gatagactat caggaaggag 97080tggtaaaaat aagttactag ttctaagaga gatgttaaga gggaccgggg aaagccttgt 97140acaaatgagt tagtagcatt ttacattata tacatctaat taagaaacaa tgcgagagtc 97200tcaccattcc tatagactct tacttgtact tgtctgaaca cgaaaactgg cttttgttta 97260taaataagct aaaaattatt ttgctccaat ttctcatgaa aataaaaata aaccttcttt 97320taacattgaa aaaatagttt gaagacagtc actcttcatt ttgtaattcc cacaactatt 97380attgaatgac tgaaattatc tttattctga agccaaaggg gtgatactga tatttcttca 97440gactactaaa aatatatttt atgaattttt agtgtgcttt atcttttttt gttttttttt 97500ttgagatgga gtttcactcc cgttgctcag gctggagggc agtggtgcaa tctcagctca 97560ctgcaacctt cgcctcccag attcaagcaa ttctcctgcc tcggtctccc aagtagctgg 97620gattacaggc acctgccccc acacccagct aattttttgt atttttagta gagacagggt 97680ttcaccatgt tggtcaggct ggtcttgaac tcctgacctc aggtgatcca cccaccttgg 97740cctcccaaag tactgcgatt gcaggcatga gccaccatgc ctggcctgag gaatattttt 97800ctaggttccc cccaccccaa gcatttattc tgcaatttta gttttgttcc taaagcaagc 97860aaggtttaag gatttaaaaa taatccgtat tttagaatgc tttctggctt tgttactttt 97920tatccacagt agaagttctc agagaatgat ctccctcttt taatttaact ttttggcaca 97980gtattttgag aattataaat aatattagaa tgttttctgg ctgggtgtgg tggctcatgc 98040ctgtaatcct ggctacttgg gaggctgagg caggagaatc acttgaacat gggaggcaga 98100ggttgcagtg agccgaggtc atgccactgc actccagcct gggtgacaga gcaagactct 98160gtctgggaaa aaaaaaaaaa aaaaaaagag tgttttcttt cctattttcc accacttgat 98220taagttactt ttcctcttaa gtattttttg ctgagtatgc tgacttaaga gtaatgttac 98280aaaatttaat ttttaaagtt ctctgaaagc ccctttatga gagttttagg ctatcaaatt 98340gtgtttaatt cttaacaatt ttttgaaaaa ttatagcttc aatatccgta cattccccac 98400aaaaaagcac taaaaatcat gccttgctgg aggctgcagg accaagtcat gttgcaatca 98460atgccatttc tgccaacatg gactcctttt caagtagcag gacagccaca cttaagaagc 98520agccaagcca catggaggcc gctcattttg gtgacctggg taagtaacta tcatttttta 98580ttaacttgta ttagaaggat ttgagtacaa tatgtgaaac ttctgtcata ggatacagaa 98640ctatataatt ggaaagtgct ttggaaaaaa tgtatttaaa ataacagcta caagtataat 98700gggtagctgt gttgtgttcc tgtaaatata gaatataaag catgcccagt agaaaaacaa 98760gcatttccag aagaaatata tctgatcact aaatataaat atatgaaaaa gatgtctcac 98820tttattactg agggaagtgc aaattaaaat aatcagttaa tgttctccta acacattagc 98880atatttttta aagtttgaca atttgaatgt cagtgaagat gcagggaaat acccctccta 98940tttagtgata atataatctg gtgaagactc tttggaaagc aatttggaaa tcagtataaa 99000atatgcatgt catttaggcc actctttcta agacctagcc ctcagatatg ctcattcata 99060tgtgcaggtg tgtatgtgtg tgtgtgtgtg tgtgtgtgtg tgtatatgta tgtatgtatg 99120tatgtatgta tgtatgttga aggctattca ttatagtatt gtttgtgata gcaaaaaatt 99180atggacaaca tataaatatc tgttataggg aaataaccaa attgtggtat acgcatgctc 99240tggagtataa tatagccatt tgtttctatt tatttatttt cttgagacag ggttttactc 99300tgttgcccag gctggagtgc agtggtatga tcatggttca ctgcagcctt cacctcctgg 99360gcacaagcca ttctctcgcc tcagcctcca gagttactag gactgcaggc atgtgtcacc 99420acacccagat aattttttaa ttttttgtag agacagggtc tcactatgtt gcctaagctg 99480gtctcaaact cctggcctca agcaattctc ccacacaggc ctcccaaagt gctgggatta 99540ccaacgtgaa ccaccacacc tggttcagtg tagccattta gaaatctaaa aaagacgtgg 99600gaaaatgtct aaggcatgtt taaatgtgag aaaagcaagt cacagtatgc atggtaaaat 99660ccgttatatt aaaataagtt cttccaaaac aaaaacatat gcaggagacc tttattttgt 99720cagtatttct tacccaaatt tctgcactta gaaaattgca tgtcatgttg tcataagttg 99780aaaaaaagat ccatgaacca atggacttct aataaaatca gtcctgcttt tgacatctct 99840ctctactttt gtgtatattc aaaccagagt gtcaatgtgt ttgtggggca cacttagcaa 99900taatacatag cagacaaaat gcatatagct cagagagtaa aattgtaagt tttgctagat 99960cactcataaa ttgctgatga gaatttaaaa tggtgcagat gctctggaaa acaggcagtt 100020tctttctttc tttttttttt tctttttgag acagggtctc actctgttgc gcaggctgga 100080gtacagtggc gtgattacaa ctcactgcag cctcaccctc ctcaggttca ggtgatcctc 100140cctcagtctc ctgagtagct gggactatag gcatgcacca ccacgcctgg ctaatttttg 100200tatttttttt tttttttttt gtagagacgg ggtttcgcca tgtttcccag gctggtctca 100260aactcctgga atcaagcgat ccacttgcgt aggcctccca aagtgctggg attacgggcg 100320tgagctactg tgcctggcct aggcagtttg tttgtttgtt tgtttgtttg tttatttatt 100380tgtagacgga gtctcacagg ctggagtgca gtggcccaat ttttggctca ctgcaacctc 100440cgcctcccag gttcaagcta ttctcctgcc tcagcctcct gagtagctgg gatgacaggt 100500gcctgccata atgcctggct gatttttgta tatttagtag atatggggtt tcaccatgtt 100560ggtcaggctg gttttgaact cctgacctca ggtgatcagc ccgcctcggc ctcccaaagt 100620gctgggatta caggcatgag ccgtcatccc tggctggtgg tttcttatga cgtgaaacat 100680gcaattacca tatgacctag cagttgcact ctgtatttat cccagataaa tgaaaactta 100740ccttccaata aaaacctgtg cacaaatgtt catagcagct taatattgaa aaactggatg 100800ttcttcagca ggtgaatgaa ctggttcatt cataccatgg aataccattc agcaataaaa 100860aggaacaaac tgttgataca tttaaccacc tggatgaata tcaagggaat tatgctgtca 100920gacaaaaacc agtccctaaa gactacatat agtatgattc cgtttggata atattcttga 100980aatagagaaa ttaagagaaa tgaaaagatt agtgtttgcc agatgttaga gacagggagg 101040tgagaggggt aagtgggtgt agttataaaa gtgcaacatg agggatcttt gtgatgttga 101100agttgtatct tggcagtgga tgcagaaatc tcaatgtgat aaaattacaa agaactaaaa 101160acaagaatga gtatagataa aactggggaa atctgaacaa gttagagtgt tgtatcactg 101220tcagtatctt agagtgatat tgtactatag ctttgcaaga tgttaccatg ggagaaacta 101280aagtgtacaa gggatctcta ggtattatta tttttttaga gatggggttt cactatgttc 101340cccaggccgg tcttgaactc ctgggctcta gtgatccgcc tgccccagcc tcctaaagta 101400ctggaattac aggcgtgagc gaccatgcct ggccctttca gtattgtatc ttagaacttc 101460atgtgaatct agcattatct catagaattt aattaaaaga aattgtaaac ctcacagaag 101520atcagaattt cctcaagttt gtgatgttga caaagatgaa ctagttgaca ctgacagtaa 101580gactgaggat gaagacacga cgtgcttcaa aaaaatgatt tgaatatcaa tggattaaga 101640agaactcttt tgacaaattg atgaaaccct cagtcagttt tataagaatg cccatcttta 101700tgatcatgct atgaaagcca atttttaaaa aaattttttg tctttcctaa caattagctt 101760gtggttataa tttaaattta gttaaatata agataaatga ttttttatta agtttagttt 101820catttttcaa ggtacgatct caaagctact ctttaaccta ctatgaatga ataatgctga 101880gttcataaca tctttgtaga tatatccaca attttccctc aggataagtg cctacaagtg 101940gaattactgg actgaaaata atgcagtttg ctaagacttt gctatctgtt cctgaatgct 102000cctccaaaaa ggttttgcca gtttacatcc tcatgaccag cgaatgagag tgttgcctat 102060tttcctgtgc ccttgttact gcttaataat ttttgaaaaa aatctaattt gacagacaaa 102120aatgcatttt atgttaattt gcttttctgg gatttttaat gaggttgagt atagttttta 102180atatttttat tggccccttt ggaactagta tcataagttt tttttcttaa gaatttatgt 102240agtctgggct gggcgcagtg gctcacgcct gcaatcccag cactttggga ggccgaggtg 102300ggtggattgc cgaaggtcag gagtttgaga ccatcctgac caacatggtg aaaccgaatc 102360tctactaaaa gtacaaaaac tagctcagcg tggtggcggg tgcctgtaat cccagctact 102420taggaggctg agtcaagaga atcgcttgaa cccgggaggt ggaggttggt tgcattgagc 102480cgagatcgcg ccattgctct ccagcctagg caacaagagt gaaaagtctc aaaaaaaaaa 102540aaaaaaaaaa aaaaaagaat ttacatggtc tgaattgcca ttaaaagaga tatgagaatt 102600attgagtaac aaataacttt ttaataattt aggcaagttt tggacgattg tactttgttt 102660agaaaccaaa agcatagtat ttgtagtttt tttatttact ttagttgcta ggaagtaaac 102720tttattcaag gtctctggta ccagttgttg ctaaaagtga ttgactaatc tgtcaatctg 102780aaattatttg ttgctgaact gctaattctt ttgcttctat cttttaggca gatcttgtct 102840ggactaccag actcaagaga ccaaatcaag cctttctaag acccttgaac aagtcttgca 102900cgacactatt gtcctccctt acttcattca attcatggaa cttcggcgaa tggagcattt 102960ggtgaaattt tggttagagg ctgaaagttt tcattcaaca acttggtcgc gaataagagc 103020acacagtcta aacacagtga agcagagctc actggctgag cctgtctctc catctaaaaa 103080gcatgaaact acagcgtctt ttttaactga ttctcttgat aagagattgg aggattctgg 103140ctcagcacag ttgtttatga ctcattcaga aggaattgac ctgaataata gaactaacag 103200cactcagaat cacttgctgc tttcccagga atgtgacagt gcccattctc tccgtcttga 103260aatggccaga gcaggaactc accaagtttc catggaaacc caagaatctt cctctacact 103320tacagtagcc agtagaaata gtcccgcttc tccactaaaa gaattgtcag gaaaactaat 103380gaaaagtgag tatgtgattt tcttgtgtgt acatatgtgt ctcactttct ttttttaatt 103440tactaagcag aacttcagat gaggaataaa atgattggaa tatttttttt ctcctctaac 103500tacttgtaaa tttgggagaa tttggagagt gtagtagagt cagatcagtg tatggaaaag 103560gagcaggagt gactggacct tctaagaagt gtgttatcag aattagtaaa tgaagggtca 103620aatgtcctac ttttcccctc cactgatttt gacatcaaac cattatccac atagccttat 103680ttcctccctc ggtcttaatt ttattaatat tttactgcac tttgcagata aaatttttaa 103740aaaattttta aaaattgcca ataagtgaca tttattaagt tcagtgctta gtgtatattt 103800ggattttatt tattagtcac aagacctttg tgcaggtagt aggcatgatt atcttttttt 103860ttttgagatg gagtcttgct ctgtcgccca ggctggagtg caatggcgcg gtctcggctc 103920actgcaacct ccgggttcat gccattctcc tgcctcagcc tcccaaatag ctgggactac 103980aggcgcctgc caccacaccc ggctaatttt tttgtatttt tagtagagac ggggtttcac 104040catgttcgcc aggatggtct cgatctcctg actttgtgat ccgcctgcct cggcctccca 104100aagtgctggg attacaggca tgagccaccg cgcccggact gattatctta tttacacatg 104160agaaaaccag ggcttagaaa ggttaggtaa cttcctctag gttgtacagt aaatgtggac 104220ctagaagcat tttgacaaga gcacctgttt ttttttcttc tctattagtt tagaaattat 104280atactcttaa ttatcacctg ggattttgat tagacagcct tcatgttctt tttcatctta 104340aatgttcttt gtgtcttaaa gggctaagtg atttcttcag atcttttagt tcactcattc 104400tcagtgaact aaaatgaggt ctaatctgct actgaatcaa gttttcagca tgttatttcc 104460ttcctccctc cctccctcct tccttccctc aaccaggctc ccgaggagct gggattacag 104520gcgcccgcca ccactcctgg ctaattttta tattttagta gagacggggt ttcaccatgt 104580tggtcaggct gatcttgaac tcctgacctc aagtgaccca cctgcctcgg cctcccaaag 104640tgctgggatt acaggcatga atcaccacac ctgacggcat gttattttca tcgcaaagtt 104700actgtaagct gggagaagtg gcacacactt gtactcccag ctactcagga agcttaaggt 104760gagaagattg cttgagccca ggagttttga gaccaacctg ggcaacacag caagacccca 104820gctcaaacaa agaaaaaaag ttattgaatt ttttatttct atggatcatt ttttgtagtt 104880tcttattcct ttcacccttc attcccactt ttgatcccat cttttattta tttagtttta 104940ttaaatgtat atttgtctga taattctgct atctacagtt ttttgtggac ctgactcagc 105000atttctttgt ttcttcggat tcagactgtt ggtggcttgt gattttagtg atttttggcc 105060gtgaacatgt ttcttggact tttgtctgtg ggaattctct gtgtactctg tataaattaa 105120gttacttcag gtgttttgca ttttcttttg ccatgcacct ggggcctggg tcactaccct 105180tctggtacca cttaaaactg aatttttgtc ttgggtgctc gtactgatcc tgtatgagta 105240caggtttata cttactgtag aaatatggtg tttgattatg gggtattgtc ccagatggtg 105300ctggagtatt aatatgctct ctgttaaact taatgtgttg tccctgtaaa actccaaaat 105360tctgaattcc agaatactac tggccccaaa tgtttaagat aagggcactg cctgtatttg 105420tttctgcctc ccactatttt ccttagttta acacaaactc acctttttaa aaaacatttt 105480gagagaattc agtattggga agagtttcta acctgtttct ggaaatggaa gtccaaagtc 105540tgtttctgta attgtttttt ttttgagatg gagtctcact ctgtcaccca ggctggagtg 105600caatgacgta ctctcagctc actgcaacct ccacctcccg ggttcaagcg attctcttgc 105660ctcagccccc tgagtagctg ggattacagg tgcccaccac catgcctggc tgatttttgt 105720atttttagaa gagatggggt ttcgccatgt tggccaggct ggtcttgaac tcctgacttt 105780gtgatctgcc cacctcagcc tcccaaagtg ctaggattat gtttctgtaa ttgtaataca 105840tttattgttt ttagaaactg tctttgcttt agtggtaatt ttcaataaaa atagaaatag 105900cagtggagtt attaaaagag cattagttac atttttccct ttttcattat cttcaaatat 105960tatatatagt aagtttgacc tttttaaaat gtatacttgt atcagtttta acacatacat 106020agattcctgt aactgtcacc actataaggg taaagaacag ttagttcctt cacctttgaa 106080gtcaagcccc acctctatcc caacacttgg caaccgctga tctttctccg tctcaatagc 106140tttgcctttt ctcttttttt ttcttatttt tttttttgag acagcgtctt gctctgtcgc 106200ccgagctgga gtgcagtgag gcaatctcgg ctcactgcaa cctccgcctc ctgggttcaa 106260gcagttctcc tgccttagcc tccctagtag ctgggattat aggcacgcac caccacaccc 106320ggctgatttt tttgtatttt tagtagaaat ggggtttcac catgttggcc aggctggtct 106380caaactcttg acctcaagtg atccacctgc ctcggcctcc caaagtgctg ggattacagg 106440cgtgagccac tgtgcccaat caggactttt tttttttaaa tttacattca acttgtcatt 106500tttttcttgt atggattgtg ccttcagagt cacacctaag agccctttgc ctaagcaaag 106560gtcatgaaga ttttctcata tgtttccttt taaaagtatt gtggttggcc aggtgccatg 106620gcttatgcct gtaatctcag cactttgaga agctgaggtg ggcagattac gaggtcagga 106680gatcgagacc atcctggcta atgcggtgaa accccatctc tactaaaaat acaaaaaaaa 106740aaaaaaatta gccgggcgtg gtggcgggca cctgtagtcc cagctacttg agaggttgag 106800gcaggagaat agtgtgaacc cgggaggtgg agcttgcagt gagccgagat cgcgccactg 106860cactccagcc tgggcaacac agtgagactc catctcaaaa aaaaaaaaaa agtattatgg 106920ttttacactt tacgtttaga tatatatctt ttttgagtta atgtcgtata agtatgaggg 106980ttacgtcaga ttttttgttt tttgtttatt tttacatatg gatgtctagt tgttctaata 107040ccatttgttg aaaagacaac ctttactcca ttgaattgcc tttgtacttt tgccatattt 107100gtctaggcct gtttttggac tcctttttct gtttcatgat gtgtgtgtct attcctttgt 107160taataccaca tggtcttaat tactgtatag taagtcttaa aattgggtaa tgctggcctt 107220ataaaacgaa ttgggaagtt tttattttta ctcttatttc cattttctag aagagattgt 107280gtagaattgg tgtcatttct tctttagata tttggttgaa ttgggaagtg atgccatctg 107340ggcctagggt tttgtttttt gtgtgtgaga cagagtctca cttctgtcac ccaggttgga 107400gtgcagtggt gagatcttgg cttactgcaa cctctgcctc ccaggttcaa gttatcctcc 107460tgcctcagcc tcccaaatag ctgggattac aagcgtgtgc caccatgccc gactaatttt 107520tgtattttta atgcagacag ggtttcacca tgttagccaa gctggtctcg aacttgtgac 107580ctcaagtgat tagcccacct tggcctccca aagtgttagg attatagatg tgagccaccg 107640tgcctggcag gggcctaggg ttttcttttt cagagtattt taaactatga attcagatta 107700tttaatagat ataggactat ttaagttatc tgtttcttct tgagtgaatt tttactgtag 107760tttatggcct ttgagtaatt aattgtattg aattgtcaaa tttatgagcg tgtaattatt 107820tatagcattt cgggtttgta gtggtatccc tcttttattc ctggtgttgg caattgtgtc 107880ttgtttttct ttgtcagatt gtatagggat ttattagtct tttcaaagaa ctagcttttg 107940ttttgatttt tctgttgttt tgttttcaat tttattgatt ttctgctctt tattatttct 108000tttctattat ttctgcttgc tttgggttta ttttactctt ttttttttct ccaagttgct 108060taaagtagaa acttagattt ctggtttgag acctttcttt tctaagataa gcatttaata 108120ctgtaaattt ccttctaacc actgctttag ttacaccccc acaaattctg gtattttgaa 108180ctgagcacaa atgaaatgtt ctaatttccc ttgaatctta ttcttttacc aatgaattat 108240ttagaaatat gttatttagt ttgcaagcaa ttggagactt ttttcctgtt atttttctac 108300catttatttc tcatttcatt atattatggt cagagaatat attttgaatg atttcattta 108360ttaattttta aaaataacat taaaaaattt tttaaaatgt gaatatacca catacagtat 108420aaagattgta cattctgttt ttggacagtt ttctataaat gtcaagttga tttagttggt 108480taatgatggt gttcagtttt tctttattct tgctgatact ttgtatgcag ttatatcact 108540ttattactca gaagagtgtt gaactttcca actacaattt ttttttccaa ttttactttc 108600agctctatct ggttttgctt catgtatttt gaggctctgt tgttaggtgt gtacacattc 108660aggatgatat cttctgggtg aattgcctgt tttatcatta tgtaattccc tctttatggt 108720aattttcctt gttctaagat cagaaatatc tgttgtccaa tttatataga cactgcagct 108780ttcatttgat tagtgcttgc atggcatatc tttttccatt tttttacttt tgatctacct 108840ttataattct atttaaaggg ggcttcttgt aggcagcata tagttgggta gtgttattta 108900tttatttatt tatttattta tttatttatt tattgagaca gagttttgct cttgttgccc 108960aagctggagt gcagtggtgc aatcctggct taccacaacc tccacctcct gggttgcagt 109020gattctcctg cctcagcctc ccaagtagct gggattacag gcacgcgcac catgcctggc 109080tgattttttg tatttttagt agaaacggat tttcaccatg ttagccaggc tcgtcttgaa 109140ctcctgacct caggtgatcc acctgctttg gcctcccaaa gtgctgggat tacaggcgtg 109200agccactgca cccggctgag tcatgttatt tttaatcttt tctcacaata cagggttttt 109260gttggtaaat ttaattattt taatataaat tttagtataa ttatttacat taaatgtaac 109320tgttgcactg gggtatttat aatgtgtaaa tataattatt ggtattaata taattatatt 109380actcataata atattaatat ctttggattt agattaccag tttagtatat gtttttctgt 109440ttctccctct ttgatttccc cttttttgct tttttttttt ttttaattct tatttttttt 109500tagtatttgt tgatcattct tgggtgtttc ttggagaggg ggatttggca gggtcatagg 109560acaatagttg agggaaggtc agcagataaa catgtgaaca aggtctctgg ttttcctaga 109620cagaggaccc tgcggccttc tgcagtgttt gtgtccctgg gtacttgaga ttagggagtg 109680gtgatgactc ttaacgagca tgctgccttc aagcatctgt ttaacaaagc acatcttgca 109740ccacccttaa tccatttaac cctgagtggt aatagcacat gtttcagaga gcagggggtt 109800gggggtaagg ttatagatta acagcatccc aaggcagaag aatttttctt agtacagaac 109860aaaatggagt ctcccatgtc tacttctttc tacacagaca cagtaacaat ctgatctctc 109920tttcttttcc ccacatttcc cccttttcta ttcgacaaaa ctgccatcgt catcatggcc 109980cgttctcaat gagctgttgg gtacacctcc cagacggggt ggcagctggg cagaggggct 110040cctcacttcc cagatggggc agccgggcag aggcgccccc cacctcccag acggggcagt 110100ggccgggcgg aggcgccccc cacctccctc ccggatgggg cggctggccg ggcgggggct 110160gaccccccac ctccctcccg gacggggcgg ctggccgggc gggggctgac cccccacctc 110220cctcccagat ggggcggctg gccgggcggg ggctgccccc cacctccctc ccggacgggg 110280cggctgccgg gctgaggggc tcctcacttc gcagaccggg cggctgccgg gcggaggggc 110340tcctcacttc tcagacgggg cggccgggca gagacgctcc tcacctccca gatggggtgg 110400cggtcgggca gagacactcc tcagttccca gacggggtcg cggccgggca gaggcgctcc 110460tcccatccca gacggggcgg cggggcagag gtggtcccca catctcagac gatgggctgc 110520cgggcagaga cactcctcac ttcctagacg ggatggcagc cgggaagagg tgctcctcac 110580ttcccagacg gggcggccgg tcagaggggc tcctcacatc ccagacgatg ggcggctagg 110640cagagacgct cctcacttcc cggacggggt ggcggccggg cagaggctgc aatctcggca 110700ctttgggagg ccaaggcagg cggctgggaa gtggaggttg tagggagctg agatcacgcc 110760actgcactcc agcctgggca acattgagca ttgagtgagc gagactccgt ctgcaatcct 110820ggcacctcgg gaggccgagg caggcagatc actcgcggtc aggagctgga gaccagcccg 110880gccaacacag cgaaaccccg tctccaccaa aaaatgcaaa aaccagtcag gtgtggcggc 110940gtgcgcctgc aatcccaggc actctgcagg ctgaggcagg agaatcaggc agggaggttg 111000cagtgagccg agatggcggc agtacagtcc agcctcggct ttcacaactt tggtggcatc 111060agagggagac cggggagagg gagagggaga cgagggagag cccctttttt gctttctttt 111120ggattatttg aatttttcct taaatttatt tatcttactt atttatttat ttttttgagt 111180gattctcctg ccacagctcc caagtagctg ggactgcagg catgtgccac tacacccagc 111240taattttttt gtatttttag tagagacagg gtttcaccat attggccagg ctggtcttga 111300actcttgacc tcaagtgatc cacctgcctc ggcctcccaa agtgctggga ttacaggcgt 111360gagccaccat gccctgcctt tttctagaat ttatatattg agttcttgat tgtatctttt 111420tatgtaggct ttttagtggc ttctctagga attacaatat acatactttt cacagtgtac 111480tcacatttaa tattttgtaa cttcaagtgg aatgtagaaa acttaaccac cataaaaata 111540gaactaggga tgaggttaaa aaagagagag aaaagaaatg taataaagat ttaataacac 111600cgtttttttt tttttttctc tttttttttt gagacagagt ctctctttct gttaccaggc 111660tggagtgcag tggcgtgatc ttggctcact gcaacctccg cctcctgggt tcaagtgttt 111720ctcctgcctc agcctactga gtagctggga ttacaggtgc gcgccaccat gcccagctaa 111780tttttgtatt tttagtagag acggtttcac tgtgttggcc aggatggtct cgatttcttg 111840accttgtgat tcgctctcct cagcctccca aagtgctggg attacaggcg tgagccaccg 111900cgcccggcta agtctttaaa tatttttttg acattgcact ttttctcttt tccttctagg 111960attttagtaa cccaaatgtt agttttgtta ttgtttggca ggttcctgag gctttcctta 112020cttctttaaa tttttttttc ctgttgttca gcttcgaaaa tttctattca tctgtcttca 112080aattcactgg ttctttcccg ttatttccat tctgttattg agtctttgta gtgaatttta 112140aattttgttt attatgtttt ttagttctaa aattttcttt ttttgtgtat gtcttatact 112200ttgctcctga aactcttatt tgtttcagga gtgatcttat ttcttagagc atggttttag 112260tagctactta aaatttgttt tatcatccca gcatatgtgt cctcttgatt gtcttttctc 112320ttgtgagata atgggatttt ctggttcttt atatgacaat taattttgga ttgtatcttg 112380gacagtttga cttacgttac atgattctga atcttgttta aatcctgtgg aaaatattga 112440agtttttgct ttaacaagca gttgacctag ttaggttcag tccacaaatt ctaagcagca 112500ttctgtcggc tctggttcca tcatcagttc agttttgtat cttatctgct tatgtgcctt 112560tctgtgtcca gtctgggacc tggccaatgg tcaggtccca aagcctttgt acacttttag 112620aagcagggcc atgcacaccc agctcacgag tggccccggg agtgcacata caactcgacg 112680ttttcatggg ctccttcttt tctgtgatgt ccctgacacg ttctgccttc taagaacctc 112740cctttatccc tttcctgttg tctggctaga aagtcagggc tttagattcc ctatacttca 112800gcacacttcc tgtagctatg tcaacctctg tggccacgac ttcttcttct tgggactgca 112860gtttctcttg tcagaaagta ggattcttgg agctgctgtc attgctgctg tggctgctct 112920gatgctgcct gggagtcgaa ggagagaaag gaacaaaaca aaacaaccca ggggatttcc 112980tccactctct ttgatccgtg agagccccct ttcctgttcc tcagaccaga aatagagggc 113040ctgtcttgga acttcttctt tgtgcatctg gtgtgcagtt tcagcttttg agtccaggcc 113100aggaggtgct ggacaaactt gtcaggagta cggaggtact gcaagttctg attacttttc 113160tcagtccacc tgcttccaag tccttggatg catttgtcca ttgttttgag ttgcattcca 113220tgggagagac agaagagtgt gcttatttca tcttgacata cttattagga tttcatatca 113280aatcaacgga tgatattctc tatattaatt tgctgttttc cctttagcaa gcacattagg 113340aaaataacac tttaacaccc gcctttggtg gtttctgtca taattattaa tacttgactt 113400tttttttttt tttgagacgg agtctcactc tgtcctttga ggcattgtcc ccataaactt 113460ttggtaaagc atcaataatt ttatctttca tccacacaag cttcaccata aatttgatgt 113520ttattcttcc attttagcag aattcatgtt gctccaatag gggctgtctt caaactgatg 113580ttttctcctt cttagtgcct cagagtagat cctgttcaga tacgttataa caggttaata 113640tgagtttatt ttggtgtaaa agtactttga aattcatgca tagttttttc atcatatgca 113700ttttccatag ctttgaacac ccccatgtaa ctctcctctt ccacaaacca aacaatgaaa 113760aagcaccttt gtgatggaag tttattttgc aataggaact cacagtgatc taagccctgc 113820tattcatgaa tataattcat tactggagtc caagttgctt tttggttttt gaagttctct 113880tcttcccttg caggtataga acaagatgca gtgaatactt ttaccaaata tatatctcca 113940gatgctgcta aaccaatacc aattacagaa gcaatgagaa atgacatcat aggtaagcag 114000tgcttgaaac tatggcaaaa aaaaaatgac aaaaaatgca cagaactgac aattttcgtt 114060attgactaag ataatttttt cttaacatgg aatttagcag ttcccttcct aatttgtttt 114120ctgagtattt tttatatcgg attatagctc actttaaaag tttctcggct gcattcggtg 114180cgagggtctt tgcctgggcc agatgggctg cagtgtagcg ggtgctcagg cctgcccgct 114240gctgagcagc cgggccggcg ggcggctacg ctaaccggca cagaccaccg gatggactgg 114300ccggcagccc cgcaccagtg cacgaagtgg gcgggacaga aacttctggg gttggaagtc 114360cagtgaggct aaaagccggt accaaagtct ctaggcatca gggctgcagc ccaagagtct 114420cacgaccagt gggcaactgg atggccagac aggtgtctca gtggtggcct ctccgtctca 114480gggcttcatc ccacttctca gtgggcctga cgtccctggg caccctggat gtctacctgc 114540attagccaga gccatcacat ggcctgtgac ttgccttttt ttgccagttg attgtgccac 114600acacagtgtc atttctgtgt catttggcac agctggaggt gcaaggagga gggcagcctc 114660atgtccagtc ccagtttcac gtaactttat tcttctgaat aaagacaatt tgctaacctt 114720aaaaaaaaaa aaaaaaaaaa agtttttctt atatgttgga cccaaattct taggctttaa 114780cctgaataac aatgacagca agatcaataa atagtacaca tttattaaac actcactgtg 114840tcccagacaa tattccaagc actttttatg gatagactca ttttaacttc taaagaactt 114900tgtgggataa atacagttat tttatagatg aagaaactga agcacagaga agttaagtgc 114960tttgtccagg gtaacagctc agatatggca gagtcaggat ttgaaactag accctcacat 115020accttaactg ctgtgctgtg gcagtgtttt tcatactgta ggttgggacc agccttctct 115080tatgccctca ccccctgcca aaaaaaaaaa aaaaaaaaaa aaatatatat atatatatat 115140atatatatat atatatatat aatatatata tatataaaat atatatatat ataaaatata 115200tgtattagta tatatgcata tatagtatat attatatatt agtatatata ctaatatata 115260atatacatat tagtgtgtgt atatatatat atactagaat aaaaaaatca aagtatctca 115320gagtagtaag gacaaacatt tcagaaaaat gttttcatta tatatacatg tatgtatgtg 115380tatgctgatt caacaaatat atttcttata ggttatagca aaatagtttg aaagctttta 115440ctgtgtttta tcaggaagac cttaggtgaa cgtatattca cagataaaag aggttattta 115500ttcattcaat aaatattaca ttctcataag tcctaatatt atgtattttt attcttcaaa 115560aaagttagta tttgtgattt atgaaataag acatgttctt gcacttttag cagatctgtc 115620ccgatgttgg gcttctttaa tccttagtgt gggtgctttg cactcactca ctgctgggga 115680cagcaagacc cctgttagtc tcagctgtgt ttcttaaatt ggcccactgt accttccagt 115740tagctattct ggggtccatg tcatgttggc tccattttcc ttttctttct cccacacaga 115800tacctataac ggctataaca taggcctggt ggctgttggt ggcttatccc tatctgcttg 115860tatttaaggg gtactgtttc actgagtttt gctgacagat gttgtcatga gatttgaggt 115920tttctgtgtt gttgctctat ttttatgtgg gaatttgcta ctatcatcat ccctagacca 115980gcttttccta gtaatacaac agggatgttc tgactgatta gagtttgcct gtttgaagaa 116040ttggttggct agtgattttt ttttgagggg agtctgtacc agttaatagc ctgactggcg 116100tgtggataaa aaggaagcag tttcaagtca aataaaacac ttaaaatgaa accacactgc 116160aactctcttt cttttactta agcttaatca aattaatgat gatgtaatcc catgaaggaa 116220aagtcttctg aaggatcaag ttgataacat tttgtgatca aagaatttga gaaaacctct 116280atcccagtgt ctatcattat atattttagg atgttaatta cctgtgtggc tttaggcaag 116340tcatttttcc tccttgagcc ccattcttaa tcctgtccaa attatttgtc tcctcttgca 116400gttggactat tttaatatag ctgtccttca agtgagtttt gttcaaagga gccttcactt 116460tagctcttac tgtgtaccca ctttgcatag tcttgtttta aatgtaatcc ttggattttt 116520ggtgttgcta actaattact gtttttatgt gaggatttag agtgatccag aatctatact 116580tgcactacct ccttcatctt ccacaaatgt ttgaagtggt agaattttta aaaactttga 116640aggtacagct gacagaattt gctgatggtt tggaagtgag tggtatgaga gggaaaaaaa 116700ggaataaagc atgactgcat tttttgtttg tttgtttgtt tgtttttgag acggagtctc 116760actctcgcca ggctggagtg cagtggcgtg atcttggctc acggcaacct ccgcctcctg 116820ggttcaagcg attcccctgc ctcagcctcc caagtagctg ggactacagg cgctcgccac 116880cacgcctggc taattttttt ttttgtattt tagtagaaac ggggtttcac cgtgttggcc 116940aggatggtct ccatctcctg acctcatgat ctactcacct tggcctccca aagtgctgag 117000gttacaggca tatatataag catataaagt gtgttatagc atacaaacag gtatatatat 117060aaacatgcag tccacacagc tgataggaat gaggcagtag tgaaggagaa gttgatgtag 117120gagaggggac agttgttaca ggaaagaagt ctggaggcag aagggatgaa ttccagtgct 117180cacatagaag attgcttaga tgggagcaag gacaatttat ctagagtcac aggaaagaat 117240gcagtacacg ggtagagatg caggtgagtt gaaagatgtg agagatgatg gaaataattt 117300tctgattgct tctatattct caaggaagca ggaagcaaag tcctcagcaa agagaataga 117360agaggtgtta aatatttgag aaaggagatg tactgtagaa aaaaaaaaaa ctcagtttct 117420ccttctgaac tctcacaaaa cagaaccctt ccatgactct agttgtgtgg ggttttttcc 117480ctgtcagcta ccaattctgc agatgattgt tcagtgaaca ccaactgggt gtcctctaag 117540tcagttcagt tctcacactg tttacctgga gatagcatca gatcccacag attgaggact 117600ctgtcccaca agactgcctc cacttcagat gccagtctca agtacaagtt gtggcctgtg 117660cttctgactg accttctata aattggagtt cccacagtcc cctccttggg ttcaataaat 117720ttgctagagc agctctcaga actcagggaa atgctttaca tatatttacc catttattat 117780aaaggatatt acaaaggata cagattgaac aggcagatgg aagagatgca tgggcaaggt 117840atgggagagg ggcacagagc ttccatgcac tctccaggtc atgccaccct ccaagaacct 117900ctacagattt agctattcag aagcccccct ccccattctg tccttttggg ttttttgtgg 117960agacttcatt atataggcat gattgatcat tggctattgg tgatcagctc aaccttcagc 118020cccctcatcc cgggaggttg gtgggtaggg ctgaaagtcc caaacgtgta attctgcctt 118080ggtctttctg gtgattagcc ctcatcctaa agctctttag aggccacagc cacaagtcat 118140ctcattagcc ttcaaaagaa tccagagatt ccatgaattt taggcgctgt atgctaagaa 118200actggctaaa ggccagttgc aatgtctcag gcctgtaatc ccagcacttt gggaggctga 118260ggcaggagga tcgtttcagg ccatgagatc aaaaccagcc tggtcaacat agtgagaccc 118320ccttacaaaa aatttaaaaa ttggccaggc gtaatagctc ttgtctgtag tctcagctac 118380tcagaaggct gaggatcact gagccctgga gttgaaggca gcagtgagcc atgatcgtgc 118440cactgactcc ggcttgggtg acaaagtgag accttgtctc agaagaaaaa ggaaaaaaaa 118500aaaactgggc aaagactaaa taacatattt cacagtatca cagatttgta ttgtctagga 118560aagtgaatgt aaacagacca ggacactagt atgatccctt ggtttcatga aggtcccact 118620aaagtcatga acacaaagtg agactaggca tcatgttata tggtttttcc agccatgttt 118680aacagctagc taaatagcta attgtttcgc tgcagtttat tttagcagtt ccttatttta 118740gcacatttca tgttttaaaa tttctaccaa taacatttta ataaactttt ttacagataa 118800cttcacaaat ccataatttt ttaagttaca atcccagaaa tagaattgct cattgaaagg 118860gtatgttcat ttttaaagtt atgctagaaa ctgccaaatt gccttcagaa aaaggtgttt 118920gtatccccac taacactagt gttagttttc ttgtgccctt gctcaagtat acatattatt 118980aaaaacaatg ttgggccagt ttactagata aaaggtgtag tgcctcctta ttctaatcta 119040tttgattact agtgagtatg tatgtctttt cacgttggtc attttatgtt tgttcctttg 119100tggattgtca tgtcctttgc tcatttttct tttggaacat ttcttagtag tttataagag 119160ctcttggtat tttaatgata gtaacctttt aactgtcatg catgctgcaa atcttttttc 119220tgtttgtttg cctttgtatt ttgtttttgg agggtttcta tgtataggaa ttaaatttta 119280tgttgttaaa tcttttgatt tctgcttttg catatgtact tcaaaagact ttctatttta 119340agatcaagtg ttacctgtat tttcttttag ttctatttaa aacctcttaa tttatatgcc 119400tgtgctgtta actcccaagt tgattcacaa gtgtgtatac atagtttgaa tttagtggca 119460atttaattat ttacaacttc ttttgcagca aggatttgtg gagaagatgg acaggtggat 119520cccaactgtt tcgttttggc acagtccata gtctttagtg caatggagca agagtaagtt 119580agttcatatt ttcacattgt gcatcctagg gaatttgggt tcattgttag gaatgggctt 119640cactcagcta aaaacaaagt atttttgaga atttaaatat tttggatatt tacaagatca 119700tataaagcat actctatctt ggttaacagt ttcttttaaa tataaattat gtgaactctt 119760aaaattttca ttttcatttt caatgttaat atttcctaag ttaaaataat ttgtttttag 119820ttctgaaata atttggggag tgattgagtc tgtagtgatt atgactatta gaattggttt 119880atttatttaa ataatgcatg tcttcagatg gctctcctaa tttgttagtt aggctttaag 119940ctaaatggat gctatataac taaatccaca tagatttgtt gaaatggctc cagaggtttt 120000ttagatttat tactgctatg tgcccttaaa aaaaatctat tcattctttc acttaacatt 120060tatcagaaga gtgctctgtg taagacgtgg ttaggcatag tgccagtctt gaaggaagtt 120120acagcctaat aaaagacata gggcatgttg tttggttact gtaatatgaa gtggcatgtg 120180ttaaatgtca ggggagaact acaaagtcat aaaaaggtgg gagagattac atacaggtaa 120240aggaatcagg aatgacacca tggggagtaa ggtagtgttg acctaggcct ttaagataca 120300atagggacag tatggaaaga gtatattttt cccacttaaa ctctttcctt ggtcgttccc 120360tcaaattttc ccttttgtcc atgtgcaggc actttagtga gtttctgcga agtcaccatt 120420tctgtaaata ccagattgaa gtgctgacca gtggaactgt ttacctggct gacattctct 120480tctgtgagtc agccctcttt tatttctctg aggtaaagtc tgcatttctt ttcacactct 120540attcgagcat tccagcctct aactatcaat gctggggccc tgtctatagg aaataacaca 120600gaagagccaa gtcatttcca aaaagatgta tcattgtttc aagttgtttc tgatggcaag 120660agtaatttaa taatatatta gagagaacat gaaaattcaa tgtattaaat aactctaatt 120720ttgagaaacc taattaaact actgcatgta agagagtgca tgtttttaat tatttggagc 120780tattttaaaa ccacagaatt tgaaacttgc ttccagtgca taaattgcag accagacttc 120840agaagagaaa aaaagtagta aattttttct tatgctcatc atttttactt tagtcacttg 120900ataggattgc ccagtgaaga agcatttgca acagacaatg agtatattaa tctttttgag 120960gcatacagtt tagtataatg ctctttgtta ggcttcaaca agtgaaatta ttttgttgga 121020aagcaaatga ctattaagta gaaagaggat tcccagtctc acaaagcagt aatttagaca 121080ctcgattctg cctctttaca agaatacagg tactcagttg atttgttttc tcactccctt 121140tctttgctat aagtttaaat caacaatttg tttaggttaa tatgtcctca tggaatggtg 121200gaaatgatca gatataaaat atttggtttg gttagtttac tctttatatg tttgctggca 121260aggaaccaca aatccagttt agtataattt ttactctagt tcactaaaag tttgcatcca 121320gctgtgtagg tagtgtttgt ttcttgttaa cttttttttc gtctaaaaga atactttaaa 121380acttttcaat ctcaaatgac tgtaacttgc tgacaggtgt taacagaaga agtagatctt 121440tttgtttttt gcttatgacc tgtattttaa tatttgagct tatagattag agattgtgag 121500agaaatctgt ttatagtctt attttccctt gtgtattttt tcttcctagt acatggaaaa 121560agaggatgca gtgaatatct tacaattctg gttggcagca gataacttcc agtctcagct 121620tgctgccaaa aagggccaat atgatggaca ggaggcacag aatgatgcca tgattttata 121680tgacaagtga gttatattga tagatggatt cagcagatac ttattgaaca tttgatatgt 121740tttgtggaaa taaagatgaa taaactcagt ctctgttgtc aaggagctca caggaggcag 121800cataaaagct gcttttatat ggtgtttgta aagctttggg ggttcttaga acaaaagttt 121860ctgctgggaa aggggaggtg tatgtggggt aaacaggatg gcaatggtgg tgttcaagga 121920gtgtttccca gaagagagat tttgtttgga tcccaaagaa agaagggaat tttgctaccc 121980agagaaggca gaaaacaaca ttctaggcaa aggcattggc ccagaagcca tggaaacgta 122040ggggaaagtg gcactttcaa gaaacttgag tttagataat caaaggagtg gggaataaat 122100atgaggatgc tggtactaat tggaatagat tgtaagggac cttgaatgcc tatttatggg 122160tatattatac tttctgtata aatctgctca ggcacgttgt taattagttt tttattagtt 122220ttcactgaaa atgagaggat ggaaacatca tacagtaaac aaaattgaaa atatctggtc 122280aggcagatga tgagcttgtg gccagctctg taacgtatgg tattcttttc atttaacttt 122340tcttactctg taaaaaaagt aattcgtggt cgggcacggt ggctcactcc tgtaatcaca 122400acactttgag aggcagaggc aggtgaatcg cttgagccca ggaatttgag accagcctgg 122460gcaacatggc aaaacccgcc tttactaaaa atacaaaaat tagctgagcg tgatggcgtg 122520cgcctgttgt cctagctact taggggcctg aggcagaagg atcacctgag ccttgggagg 122580tcgaggctgc agtgagctgt gatccactgt actccaccct gggcagggca gtagagtgag 122640accctgtctc caaaaaaaaa aaaaacaaca aaggtaattt gttatttgta tccttaagca 122700aatgctaaag gggtaacttg gggatagaga aaagtccaca gatgttaggg tttgaagaca 122760ctaatagtat ctaggccagt ggttcctgaa cattagtctg tgggctcttg ctgggctgtc 122820tgcataggaa tcacctgaga gcttattaaa aataggtttt caggctggtt gcggtggctc 122880acgcctataa tcccagcact ttgggaggct gaggcaggcg gattacttga ggtcaggcgt 122940tcaagaccag cctggccaac atggtaaaac cccgtctcta ctaaaaatac aagaattagc 123000caggcatgat ggcacacacc tgtaatccca gctactcagg aggctgagga aggagaattg 123060ctcgagcccg ggaggtggag gttgcagtga gcggagatca tgccactgca ctccaggctg 123120gctgacagag ggagactctg tctcagaaaa aaaaaaaaaa ataggttttc agtctgggta 123180ccggtggctc acacctgtaa tcccagcact ttgggaggcc aaggcaggca gatcacttga 123240ggtcaggagt ttgagaactg cctggccaac atagtgaaac cttgtctcta ctagaaacta 123300caaaaaatta actgggcatt ttgacgggtg cctataatcc cagctactag ggaggctgag 123360gcaggagaat tgcttgaacc cgggaggcag aggactgcat ctcaaaaaaa aaaaaaaaaa 123420aaaggtttcc agtccccctg tctcagaaat tctgattctg caggtttgag gtgtgaccag 123480gaatctttat ttttagaaga cataccagat aattctgata aatagccagt ttagggatgt 123540agtctaattt tcctattttg caagtaagga aaataaggcc cagagaggta atgattttct 123600caaagtcaca gaacaagtta gtggcagaat ttggactgga atgcagttct taatgttctg 123660tccagtgttt attctggtac agtatgtttg tagaaggtat tacgtaagaa acattgttat 123720atagatgttg agataggaag agtttacatt tagaaatttg gtctaaaatg cctgaacatt 123780caagtcgtgg aggagtattg accaacttac tcaatacaac ataggagatt cacattttgt 123840tacaaaaatg ctgatttaaa aggagagttt tctttttttt cttctttttt attttttgag 123900atggagtctt gctctgtcac ccaggctaga gtgcagtgac acgatctcag ctcactgcaa 123960cctccacctc ctgggttcaa gcggttctcc tgcctcagcc tcctgagtag ctgggattac 124020aggtgggggc caccacgccc agctaatttt tgtattttta gtagagacag ggtttcacca 124080tgttggccag gccggtcttg aactcctgac ctcaagtgat ccacccacca ctgcctccca 124140aagtgctggg attataggcg tgagccactg tgcccagcct gcttgttttt gtatcatata 124200tatgcatcat cataatcatg cattatcaac ctttgtattt ctgtcaggac atagaaacca 124260ttagagtgct tggaagagag cctttttttt tttctcgcat ttaatgcttt ttttggtatt 124320catttcataa tcagcttacc aaaacattac ctgcattata ccccatcaag gtagaaatct 124380ttgtgttatc aatattggtt actccctttc cacaccgagt catcagtaag tcctgttcta 124440tccaaatagg tcatatgcat ctagctcacc cctcagtgct gttttgtttt gaatttgtac 124500atgtttactc ctgatgcctt gtagttatga tgatgtgttc ttattttatt ctgtgcatac 124560aagttctcag ctcgcttttt agggaaaatg accatgtctt cctttcctat aaattccttt 124620ctatctatca agtcctcaac agagaatagg tacccataaa tatgtgattg ttagtttctt 124680tgcctcagtt gtagtctgat ccttacagct tttaaacaac agtagagttc accgtcaaga 124740actaaggatg gttggcaggc agatagaaag gtagcaagtt gacccaacta tctctgggga 124800agtgggaaca aagaaaggtt acatcagcac tgtcatcaca tagctctata gttctaggcc 124860tgcaggctca atcaagtagc cttgtataag attctctgga ggaggtgctg aaagttgctt 124920atacttgcta tggaatttga ttttacttcg gatatctttt taccataggt acttctccct 124980ccaagccaca catcctcttg gatttgatga tgttgtacga ttagaaattg aatccaatat 125040ctgcagggaa ggtgggccac tccccaactg tttcacaact ccattacgtc aggcctggac 125100aaccatggag aaggtaaccc agaacttcaa acgtatcaaa ctacaagaag ttttattggt 125160agaactcata aaatataagg tgggaaaacc aagcagaata gcacagtgga aattgaagca 125220gtccagcaaa gtgattaaga gcagaggcct tgagtctggc ctggtatgta cagtcacgtg 125280ccacataaca ttttagtcaa cagtggactg cgtgtacgat ggtcctgtac gattataatg 125340gatcaaagct ggtagtgcaa taataacaaa agttagaaaa aataaatttt aataagtaaa 125400aaagaaaaaa gaaaaactaa aaagataaaa gaataaccaa gaacaaaaca aaaaaaatta 125460taatggagct gaaaaatctc tgttgcctca tatttactgt actatacttt taatcattat 125520tttagagtgc tccttctact tactaagaaa acagttaact gtaaaacagc ttcagacagg 125580tccttcagga ggtttccaga aggaggcatt gttatcaaag gagatgacgg ctccatgcgt 125640gttactgccc ctgaagacct tccagtggga caagatgtgg aggtgaaaga aagtgttatt 125700gatgatcctg accctgtgta ggcttaggct aatgtgggtg tttgtcttag tttttaacaa 125760acaaatttaa aaagaaaaaa aaaattaaaa atagaaaaaa gcttataaaa taaggatata 125820atgaaaatat ttttgtacag ctgtatatgt ttgtgtttta agctgttatg acaacagagt 125880caaaaagcta aaaaaagtaa aacagttaaa aagttacagt aagctaattt attattaaag 125940aaaaaaattt taaataaatt tagtgtagcc taagtgtaca gtgtaagtct acagtagtgt 126000acaataatgt gctaggcctt cacattcact taccactcac tcgctgactc acccagagca 126060acttccagtc ttgcaagctc cattcatggt aagtgcccta tacagatgta ccatttttta 126120tcttttatac tgtattttta ctgtgccttt tctgtatttg tgtttaaata cacaaattct 126180taccattgca atagtggcct acgatattca ttatagtaac atgtgataca ggtttgtagc 126240ccaaaagcaa taggttgtac catatagcca aggggtgtag taggccatac catctaggtt 126300tgtataagta cactctgtga tgttagcaca atggcaagca gcctaacgga aattctgttt 126360attgattgat tgattgattg attgattgag acagagtttc actccattgt ccaggctgga 126420gtgcagttgc acagtcttgg cacactgcaa cttctgcctc ccaggttcaa ccaattatcc 126480tgcctcatcc tcccaagtag ctgggattac aggcaggcac caccatacct ggctaatttt 126540tgtattttag tagagacagg gtttcaccat tttggccagg ctgttctcga actcctgacc 126600ttaagtgatc tgcctgcttt ggcctccgaa agtgctggga ttacaggcat gagctaccat 126660gcctgggcag taactgaaat tctctaatgc cattttcctt atctgtaaag tgacgataat 126720atgcacgttt acctcaaagt tactttgatg attaaagtaa ggtaatgtat ataaaataca 126780tattaacata gtacctgaca catggtaagc atcaaaaaat gttaactact tttattacta 126840ttattattac gtatttttaa ataattagag agcagtatca aaaattagct gggcgtagtg 126900gcatgcacct atagttccag ctactcagga ggctgaagct ggaggattgc atgagcctgg 126960gaattaaagg ctgcagtgag ccgtgttcat gcccctgcac tccagccttg gtgacagagc 127020aagaccctgt cttgaacaat taaagaaggc attatgccgc aacgttagct tagaaatgat 127080ccacatatat caccagtaac tgtcaacagg attggaaccc tagttttggg tattatgatc 127140acaaggtatt attaatagct tattaataat aaagcgttgg ctaggcacgg cgactcacat 127200ctgtaatccc agcactttgg gaggccgagg tgggtggatc acctgaggtc aggagtttga 127260gaccagcctg accaacatgg agaaacccca tctctactaa aaatacaaaa ttagccgggc 127320gtggtggtgc atgcctgtaa tcccagctac ttaggaggct gaggcaggaa aatctcttga 127380acccgggagg cagaggttgc agtgagctga gatcgcacca ttgcactcca gcctgggcaa 127440caagagcaaa actccgtctc aaaaatataa ttataataaa taaataaaag taaagtattg 127500atgtttgtga atgatttatt cttctaatga actagaggag atttttccag gaatttcaga 127560gccagtgagg ttatgttgct tgtatgtgtc atgtgtatcc aggtgaaaaa acttaattaa 127620acgctattat ataataccat acataaaaac tgaattttag gaatactgaa gaatgacata 127680tagaagtcaa atcattaaat agctagtagt aaacagaata gagtgtcagc tgttacccaa 127740tgatgataat attttcacga ttaaaattaa accttttctg attttaaagg aaaagttcag 127800atctgtatca tataaagaat gtaaattttc agggtaataa aattaaaatg cagagagaaa 127860aatgcaaaaa tagttcttac tagatgtgtg tatgtaagga acttagacta attttaagaa 127920cactgtcaag accctggtag ttaggtagga aaaaagacat gaatgattca ttcaacaaaa 127980actttgagta tttctgtgct agatggtagt gttacagtgg taaacaaaat aaatgtgttt 128040ctgctatcct ggagcttagt ctacaaaaaa ggtacatatt ggccgggcac ggtggctcac 128100gcctgtaatc ctagcacttt ggaagatcga ggcgggtgga tcacctgagg tcaggagttc 128160aagaccagct tggccaacat ggcgaaaccc cgtctctact aaaaatacaa aaattaactg 128220ggtgtggtgg cggacacctg taatcccagc tactcgggag gctgaggcag gagaatcact 128280tgaacctggg agacagaggt tccagtgagt cgagatcatg ccactgcatt ccagcccggg 128340ggacaaaagc gaaaatacgt ctcaaaaaaa caaaaacaaa caacaaaggc acgtattaaa 128400tacgaacata aatatttaca aattatactg aataagttct catgtttatt atttgcttgt 128460ccagttacaa acttttcctt cgtagaatta gaaatataaa taataaacat gagaactcat 128520tcagtataat taataattat taaatgtaaa taaaaacatc tatgtacaat taggcattta 128580tttaagaatt atttgaaaaa aaaacaatgt ggaaacagat attttgatat attgctagtg 128640attgaaattg ataatgttct tttgaagagt aaagtgacca tatatattaa agttaaaatt 128700taactcagca atcacacgcc tggtgagtta tcttaaggaa atcagtttga aagtaaaatc 128760aatatatgca caaagacttt aacatttatc ataaaccaga aaaatcgagt ttcaaattat 128820atcctatgga ctattttctg ctaaaaagta ttaatatcaa ctttatgtaa tactttcgtg 128880acaaatattt tgggggagaa aacccaacaa aattacatgc attgtaattt tttttttttt 128940ttttttttta gacagtcttg ctccagcgtc caggctggag tgcagtggtg caatctcggc 129000tcactgcaac ctccatctcc caggttcaag caattctcct gcctcaggcc tcccgagtag 129060ctgggattac aggcgctcac caccatgcct agctaatttt tatagttttt agtagagatg 129120gggtttcatc atgttggcca ggctggtctt gaactcctgg tctcaagtga tccgtctgcc 129180tcggcctcct agagtgctga gattacaggt gtaagccact gcacccagcc ttatgcatta 129240taattttaat ttgtaaactg tacaaaggga taatacttgt agtacaacaa gaagtaaaaa 129300catttgttat aggtagttaa catttgtaac cagtagaatt ataggtaaaa tttatttatt 129360taaaacagtt ttagttggat ttgatttcaa ctttaaaata atgcttttca tctctatcag 129420gtctttttgc ctggcttttt gtccagcaat ctttattata aatatttgaa tgatctcatc 129480cattcggttc gaggagatga atttctgggc gggaacgtgt cgctgactgc tcctggctct 129540gttggccctc ctgatgagtc tcacccaggg agttctgaca gctctgcgtc tcaggtattg 129600actgattgcg tctgccatta gggagaaaag catacacatc ctttccttca catcccagta 129660acagatccta ttatttgtaa attttaagtt gtggaaaaaa aagataaaag ccaggcacag 129720tggcctgtgc ctgtaatccc agcactttgg gaggctgcgg tgggcggatc acacgaggtc 129780aggaattcga gaccagcctg gccgacatgg tgaaacccca tctctactaa aaatacaaaa 129840attagccggg catggtggca ggcacctgta atcctagcta cttgggaggc tgaggcagga 129900gaatcgcttg aacccaggag gcagaggttg caatgaacca aaatcacgcc actgcactcc 129960agcctgggtg acaaagtgag actgtgtctc aaaaaaaaaa aaaaaagaga gaaataaaat 130020tagcctactt actatcttct aatcaaagca tttgtggtaa cttaaaatat actgtattgt 130080aaagtatcat gctgtttcat ttaggccatt attctatttg aatctgtggc tgtttctctt 130140aataaatcaa gtaatatgga atatattcat agcctctgaa gagctcttta tgtaagtatt 130200tatttaggat actttttgta aaataagtga atgaattctt aggtctcctt tttttttctt 130260ttcttgagac agggtctcct cgctgcaacc tggaaattct gggctcaaat aatccaccca 130320ccacagcctc ctgaatagct gggactagag gcatgcacca ccacgcctgg ctaatttgaa 130380attttttttt ggccaggcat gatggttcac gcctgtaatc ccagcacttt gggagaccga 130440ggcaggcaga tcacgaggtc gggagatgga gaccagcctg gccaacgtgg tgaaaccccg 130500tctctactaa aaatacaaaa attagctggt tatggtggct catgcctgta atcccagcta 130560cttgggaggc tgaggcagga gaatggcttc aaccagggag tcggaggttg cagtgagccg 130620agatcacgcc actgcactcc tgcatggtga cagagtgaga ctccatctca aaaaaaattt 130680tttttttaaa tgatggagtc ttgctgtgtt gctcaggctg gtcttgaacc cctgacctca 130740aatgccgcct gcttcagcct aagtttcttt tttttttgta aagagacagg gtcttgctat 130800gttggccagg gtagtctcaa actcctggct tcaagcagtc ctcccacctt ggcctctcaa 130860agtgctggga ttacaggcgt gaaccactac ctataatgtt gtgtttcact caaggccttt 130920tgatttcgtt ttgcattacc gtgccacatt gtgcatttcc ttgacctttt ttgggttttt 130980tggagtgctt tcatatgtta aaccatacct gattctcctc aaaatcacac aaagtagaat 131040atcctaagac aagaaatcta aggaggcata aagaagttaa ctggttttat taaactcaca 131100cagtaaatga tagagccaga aatattcccc ttctagtgtt cttcaccatc agcttaatgt 131160agcataataa ttttctaatt actgttgaca aataaataac cctttgaatt ttcaatactg 131220ggccttggat aaattttcct aatttgtaag agagtattat cgtattgcca tttacaaagc 131280tctcctgagt atctttttct tctgttaagt ttacctagga gataaactgc tgagtatggt 131340tgccattttg gttttttgat ataggttaga atgtcttggt tttttttttt tttttttttg 131400gtttttgttg ttgtcattgt ttgagacagc atcttgctct gtcgcccagg ctggagtgca 131460atggcacgat cgtggctcac tgcaacctcc acctcccggg ttcaagcaat tctcctgcct 131520cagcttcctg agtagctggg attacaggca tgtgcaacca cacctggcta atttttgtgt 131580ttttagtaga gaaggggttt caccatgttg gtcaggctgg tattgaactg ctgacctcat 131640gatccacctg cctcggcctc ccaaagtgct gggattgcag gcatgagcca ctgcacctgg 131700ctgaatgtct tgtttttgat taggcactta agaaaggcct aggtactaac cataaaatat 131760atttttatac cttttgttga tactatatat atagaaaact gcacttatca taaccttaga 131820caccttgaag aatgttcaca agcagaacta acccatgtga cccagcatcc agatcaaaaa 131880cagcattatc agcccctcta gaagccctct tgggcccctt ccattcactg tccttcttgt 131940caccagggta gctactatcc tgacttttga tggcatagat tagcattacc tgttcttgtc 132000attttataaa taaaaccata ctgtgtattc ttttcttgta cagctttatt gtgctaattc 132060acatttacat catacaattc agtggttttt atatggtcac agagttaggt aaccattacc 132120acatcgattt tagaacattt ttttcactcc agatagaaac cccctttact taaactccaa 132180atcccccact ccaccagccc taggcagcca ctagtctact ttttatctct atagagacaa 132240tagatttgct tattctggac atttcataaa catggaaccg tatattatgt ggtcttttgt 132300tgccaactgt ctttcactta gcatcatgtg ttcaaaagag catcatgtta tccatgtttg 132360gcatgtatca gaattttatt cctcattatg gccaaatatc ccattgcaag gatttatgac 132420attttatttg aattgtaccc tcctttctgc catttatcaa taatgctact gtgaccattt 132480gtgtacaagt ttttgtgtgg atacaggttt tctttttgtt tttaaatttg aggtggagtc 132540ttgctctgtc gcccaggctg gagtgcagtg gcacaatctc ggctcactgc aacctctgtc 132600tcctgggttc aagcagttct cctgcctcag cctcccgagt atctgggact ataggcacgc 132660accaccacgc ccagctaatt ttttagtaga gatggggttt caccatgttg gccagtctgg 132720tctcgaactc ttgacctcaa gtgatccacc catctcggcc tcccaaagtg ctgggattac 132780aggggtgagc cactatgccc ggctgtggtt ttcatttctt ttgttgtata tacataggag 132840tagaattgct gagtcaagag gtaactctta aacttattga aaaactgcca gattgttttc 132900cgaaaaggct gcaccatttt gcaatcccac cagcagtgta tgagttttac agcttctcca 132960catttcattg gaacttatta tctgtttggc tgtttttaaa aatgatagtc attccaataa 133020gttctacttc agtgtggttt ttgcacttct ctgatgagta atgatgttga gcatcttttc 133080atttgcttat tggcctttgt tctagctttg gaaaaatgtt tattcaaatc ctttggccat 133140ttttattttt atttttattt atttattttt ttttgagacc aagtctcact ctgtcagcca 133200ggctggagta caatggtgtg gtctcagctc actgcaacct ccgcctcctg tgttcaagtg 133260attctcctgc ctcagcctcc cgagtagctg ggattacatt tcaggcacct gccagcatgc 133320cgggctgatt tttgtatttt tactagtgac agggtttcac catgttagcc aggctggtca 133380caaactcctg acctcaggtg atctgcctgc ctaggcttcc caaagtgctg ggattacagg 133440cgtgagccat tgggcccagc ctagattttc ttttttcttt ttttttttga gaaggagtct 133500tgctcttgtt gcccaggctg gagtgcaatg gcacaatctt ggctcactgc aacctctgcc 133560tcctgggttc aagcgatttt cctgcctcag cctccccagt agctgggatt acaggtgcct 133620accaccacac ccagctaact tttgtatttt ttttagagac agggtttcac catgttggcc 133680aggctggtct caactcctga cctcaggtga tccacctgcc ttggcctccc gaagtgctgg 133740gattaccggc atgagctacc aggcccagcc aattttctca ttatattgcc caggctggtc 133800tcaaactcct gggttcaagt gatcctcctg ccttggcctc ccaaagtgtg gggagtacag 133860gcgtgagcca ccttgctcag cccctttgcc catttttaaa ttagattgcc tttttatatt 133920gagtttcagg agtcctttat atattctaga taaatgtccc ttatcaaatt atattatttc 133980caggtatttt cttcattctg tgagttgtct ttcctctacc ttttaaaaaa ggtgggtttt 134040tgtttgtttg tttgtttgtt tttttaagat aaggtctcat tctgctgccc aggctggagt 134100gcagtggcac aatcacagct cactgccacc tcaacttcct gggccgaagt gatcctctta 134160cttcagcctc ctgaatagct agggccatag atacacacta tcacacccag cttttttttt 134220ctgtttgtag agacagatct tactgtgttg cccaagttgg tctcaaactc taggctcaaa 134280gtgattctcc cacctctgcc tcccagagtg ctgggattac aggtgtgagc cacacgcaac 134340ctgtcttttc actattaata gtgtcttcct gcttcagcct cccgagtagc tgggattaca 134400ggcacccacc accatgcctg gctaattttt ttgcattttt agtagagaca gtgtttcacc 134460atgttcaccc ggctggtctt gaactcctga cctcaggtga ttcacctgcc atggcctccc 134520aaagtgctgg gattacaggc gtgagccact gcacccggcc aaaatattgc cttcttaaca 134580gtattgtctt ctaatttgtg aacatggatg tatcttcatg tatttatgtg ttctttcatt 134640tcagcagaat tttgtagttt tcagagtaga agcctttcac ctccttgggt catttattcc 134700tatgttttaa gttcttttcg attccattat aaatagaatt gttttcttaa tttcattttc 134760agattgtttg atgagagagc atagaaatac aagtgatttt tacatgttga tcttgcaact 134820tcaactttga taaatctgat tgttagctct aatagttttc ttgtggattc tttaggattt 134880tcaatatata agatcatgtc atttatggat agagatagtt ttttttctgg ctagaactta 134940cagagcaatg atgagtagaa gtggcagaag caaaaatctt tgtcttgttt cctatctgac 135000agggaaagct ttcagtttca tcatttaata tgatgttagg tgtgggtttt caataaatgc 135060cttttttcag attcaggaat ttccctatca ttcctgattt tttaaggctt tttttttttt 135120ttaaatcatg aaagggtgtt gaatattgtc atgttctttc tgtatcagta taaatgatcc 135180tatggatttt gggttttatt ctgttgatgt gaaatattaa ttgattttca gatgttaaac 135240caaccttgca tacctgagat gaatctcact tggtcatggt gtataatctt ttcaatatgc 135300tgctggattc catttactgg tattttgttg aagattttgt atctgaacgc ttaagataac 135360atttacactc tatcagaaat gaattgacca taaatgtgag agtgtatttg tgggttcttg 135420attctcttcc attccaaaga tagacataca tccgtctgta tgtctgtctt tatgccagta 135480ccatactctc ttgattacta ttgctttgta ataagttttg aaatcagaaa gtataaatga 135540gattttggta tctgagtaac agtcctcata gaattagttg ggaaatattc cctctttatt 135600ctggtccctc tttctttttt gtttaactgt gtatcttgga gattgttcct tctcaacaca 135660tgagagccgc tttccctacc ctcccacccc tgctatagag aggtctataa gtgtctgttc 135720aattatttta tttacttaac ctattactta gtcggggaca ttaagcttgt ttatgtcttt 135780tattttaaac aatgctgcag tgaataatct tgtatataag tcattttcca tcaatataag 135840tctctctgta actgaatttt tagaagtgga atttctaggt caacctatgg ctctgtattt 135900cacaaaaata ccaattctgg tttttcttgt ggaggtgggg agtaggaggt agaatgctgg 135960aggagaactt gctgtactca gctggctagt cattttagaa aggtttcctt agcttctttt 136020tgtcatatgg cctcaccaag aatcaaaaac attcctattt accctgtaaa catggggctt 136080tactacccaa gatacatatt tctggatgta tgacagcttt tcatattgaa gaaataatgc 136140tgtgagtaca gcacatttgt tggaacttag gtcgttaaga atgtcttata aattcataca 136200ttatacattt tattttattt tattttttag tttttgatac agagtcttcc tctgtcgccc 136260aggccagcgt gcagtggtac aatcttggct cactgcgacc tccatctcct gggctcaagt 136320gattctcatg tctcagcctc cagagtagct atggttacag gcatgcacca ccatgcccgg 136380ctaatttttt tatttttagt agaaactggg tttcaccata ttgaccatgc tggcctcgaa 136440ctcttggcct caagtgatcg gcctgcctca gcctcccaaa gtgctgggat ccttgtattg 136500ggtaaaagat gaatattgag ggctgcatgg tggctcatac ctgtaatccc agcactttct 136560gagactgagg tgggaggagt cctggagccc aggagggtga ggctgcagtg agttgtgatc 136620gcgccattgc acttcaacct aggaattata ggcttcagtc actgtgcccg gcatgtacat 136680tttaatattg tgctttcctc ttttagctat agtatgaggt tacatttcag agtcattgtt 136740gttaagcatc ttaatagtga tgaggttgag tgaaagttac ttctatttca aacactgaag 136800aaaattttgt acaaatctgt cacattccaa gcccaggact gattgtttca tatacttcta 136860attttacaat ttctattgta gtccagtgtg aaaaaagcca gtattaaaat actgaaaaat 136920tttgatgaag cgataattgt ggatgcggca agtctggatc cagaatcttt atatcaacgg 136980acatatgccg ggtaagctta gctcatgcct agaattttta caagtgtaaa taactttgca 137040tcttttaaat tttttaatta aattttacat ttttttctaa tctattatta tatgcccaga 137100actttcactt agagtgtgca gtataatgtg gtggttaagt ataaaggctc tggagtgact 137160tcctgggttt taatcttggc tctgccattt attggcagcc gctaacctct tggtatctca 137220gtttcttcat ctgtaaaatg agaataataa agtgaaaaga tgccaacatc atttactctg 137280ggctgcataa ctgatacttg gaaaaagtat tcctttgagt ttaagaatta agttggttat 137340tcattttagc ttgtaataaa aagatagtga ttcataggat atgccactta ctgaaattta 137400ccacagatcc aatcataaaa tcactttctc ttccctaaag atagcttgat taacatgtaa 137460aggtgtgtaa aggcttgatt acactaccct gatccgtacc ccagttccca gcagcaccat 137520gaaaaaggga tttcaacata tttaattact ttcagtagaa agtaacagtg gtaggccagg 137580cgcagtggct cacacctgta atcccagcac tttgggaggc cgaggtgggc ggatcacgag 137640gtcaggagat tgagaccatc ctggctaaca cgatgaaacc ccgtctctac taaaaataca 137700aaaaattagc cgggcatggt ggcaggcacc tgtagtccca gctacttggg aggctgagac 137760aggagaatgg cgtgagcccg ggaggcggag cttgcagtga gcttagattg tgccactgca 137820ctccagcctg cgcagtggag cgagactctt gtctcaaaaa aaaagaaagt aacagtggta 137880ttgggagact gaggagccta gaaagtactt gaaggaagta aaaggtttgt ttgaccacat 137940tgtatttgga aagccagctt tttcagctgt gtcagctttg tgtagtgatt tttagttctt 138000cttttagaaa ataacggaca aggccgggca cggtggctca cgcctgtaat cccaccactt 138060tgggaggccg agacgggcgg attacctgat ctcaggagtt cgagaccagc ctgggcaaca 138120tggtgaaacc ccgtctctac taaaatacaa aaagttagcc gggcgtggtg gcgtgtgcct 138180gtagtcccag ctactccgga ggctgaggca ggagaattgc ttgaacccgg gaggcggagg 138240ttgcagtgag ccaagatcac accattgcac tgcagcctgc gcgacagagt aagactctgt 138300ctcaaaaaat aataataaaa taaaaaagaa tggacagtaa acctaaatga gttcattccc 138360aaagatgatg ttattcttaa gggatggttc atttatttaa gaccttacat aaagtctatc 138420aattgcgtga tttttcactt ctgtaattgt gtgtatgtat aatgtaaata tatatgtttt 138480tgttttgttt tggttttttg agacggagtc tcgctctgtt gctcaggctg gaatgcagtg 138540gtgcaatctc agctctctgc aacctctgtc tcccaggttc aagcgtttct tctgcctcat 138600cctcccaagt agctgggact acaggcacgt gccaccacgc ccggctaatt ttttgtattt 138660ttagtagaga tggggtttca ccgtgttagc caggatggtc tcaatctcct gacctcgtga 138720tccacccgcc ttggcttccc aaagtgttgc tattacaggc atgagccacc acacccagca 138780tgtatttttt aaatgtataa aatgaagcag aaaagagaaa tgataatttt tcttcatctt 138840gaaagattat cttcaccagg cgcagtggct cacacttgta atcccagcac tttgggaggc 138900ctcggcaggc ggctcacttg agttcgaaac cagcctggcc gacatggtga aactccgtct 138960ctactaaaaa taaataaata aagatggttt taatatatgt tttagtttta tgattttagc 139020atctttctga aatttttctc aaggcaagta aatttgtatc agttggtata ttggtaccca 139080tctatgaaat aacttattag gaagatatct ctaaaataag atcactttgc ctaaaataaa 139140ctgatatatt gatgttcaca gaatttttct tttaaccgac ttgataaatg cattattctt 139200gacgtcaagt gatccacctt cctcagcctc ccaaagtgct gggattacac acatgagcca 139260ccgcacctgg cattattctt ataaaaggtt aaatttctag ttaagtttaa tgtcctcttt 139320gttcatgtac cattgcttat tttcttccct tcctactcac agtaatcatt cttatggtat 139380gcacttttgt ttgcttattt ttatgtaatt gatattacgc tccattctgt acgttgtact 139440ttcattcaca gtgagttttg gacattccta tgttcatcta tacagactta cttcatttta 139500actacactgt agtattccgt atgtaatatt tactataact catcactgta gcagagcatc 139560tcatagtgta tgtattactg ttttgccatt ttggtatcaa tgagtattta agtcatttgc 139620agtttttccc tcttataccc agtattacag aggatctctt tttatatgct tctttgtacc 139680aagaggcaga ttaaaaaatt tttttttgaa aaaatttttg aaaaaaaatg aaatgaagtc 139740tcactatgtt gcccaggctg gtctcaaact cctaggctca agcaatcctt ccatcttggc 139800ctcccaaagt gctggggtta caggcatgag ccaccatgcc tggcctacat tttaaatttt 139860gatagctctt acaatttact ttgtaaagta tctgcatcat tttatgttct caccagtctt 139920taataagaat acttcatact tttggctgga cacagtggct cacgcctgta atcccagcac 139980tttgggaggc cgaggcgggc agatcaagag atcgagacca ccctggccaa tatggtgaaa 140040ccctgtctct actaaaaata caaaaattag ctgggcgtgg tggcgcaccc gtagtcccag 140100ctactcgaga ggctgagaca ggagaatcac ttgaacccgg gaggtggagg ttgcagtgaa 140160cttagatcac accactgcac tccagcctag caacagagtg agactctgtc tcaaaaaaaa 140220aaaagaatac ttcagactta attttttttc cagtcttaag tgtttgctaa tgagattgag 140280tttcttttgg tatgtctctt gattgttcag gttttttctt ttatgaattg actgttcatc 140340tctttttcac attatttctg ttgggtgatt ttattagtga cttgttaaaa ttctgtatat 140400tttttcagca tgacacttca ttattcaaaa aaaaaaaaag attctctatg tttctcgata 140460ctaatcattg gttggtaata ccttaaaaat aagaccctta ctgtattttt tgcttttttt 140520tttttttttt tttttttttt tttgagatag agtcttgctc tgttgcccag gctggagtgc 140580aatggtatga tctcggctct cagctcactg caactgcaac ctctacctcc ctgtttcaag 140640caattctcct gccttagcct cccaagtagc tgggattaca ggcatccacc accacaccca 140700gctaattttt gtatttttag tagagacagg gtttcaccat gttggccagg ctggtctcaa 140760actactggcc tcaagtgatc cgcctgcctc ggcatcccaa agtactggga ttacaggcat 140820gagccacagt gcctagccac tttttgcttt ttaactttgt tttatagtac tatagtttta 140880gtataaacag atgtatgtat acacacaact atggctttat aatatgtttc agtcattgtt 140940agagcaaggc ctaccttttg ggtgcttctt ttacaaaatt gtcttggcta ttcttgtgcc 141000ttttttctta tttgtgaatt ttagaattgt gaattacctg ttgactcacc atgttttgta 141060aactgaggat tttgaatgga attgcactca attaaagatt atcttgcttt ctgtgcagca 141120atgttttatt tcaaataatc cctactttaa attacttagg atagctataa attgtgtttc 141180tggctttcta gatttagatg aaacgcttta aattgattgt tttctcctaa atttaaaact 141240gattgttaga agttaaagtc ttctgttcat tcttatttag gaagatgaca tttggaagag 141300tcagtgactt ggggcaattc atccgagaat ctgagcctga acctgatgta aggaaatcaa 141360aaggtttgtg gtgtttttat acttcatatt aagcctttac tcacattagt gattgactgt 141420aagtcaaaga ccacttaagg tttaaactgt ttattttgta aagtaaccac tgtatctttc 141480accttgtgtt tatagtcaga agtaagtaca agggcttcct gtagtcacat ctttatgcaa 141540tctcctctga atcaaaagtt agtgaacttg ctttgccact ccagaaggca catgaatatg 141600aaaaagcatt gtctattttc ttatttaatg gcaaaatacc cgacctaagt tggacttaat 141660gtttgagacc gtttatttta ttaaattata ttttttctct tttctttttt ttttttgaga 141720cagttcttgc tctgtcaccc agaccggagt gcagtggtct gaccgcacct cactgcaacc 141780tctgcttcct aggttcaagc gattttcctg cctcatcctc ctgagtagct gggactacaa 141840gtgcgcacca ccacacctgg ctaatttttg tatttttagc agagatgagg tttcaccacg 141900ttggctaggc tggtctcata ctcctgacct caagcaatcc atccgccttg gcttcccaaa 141960gtgctgggat tacaagtgtg agccaccatg cctggcctta ttaaattatt tttattaaat 142020ttcctcaaga ttgatgaaag taatgaaata taaaagtaat gaaatatatg tggaaaatag 142080actggattaa gaaaatgtgg cacatataca ccatggatac tatgcagcca taaaaaagga 142140tgagttcatg tcctttgtag ggacatggat gaagctggaa accatcattc tgagcaaact 142200gtctcaagga tagaaaacca aacaccgcat gctctcactc ataggtggga attgaacaat 142260gagaacactt ggacacaggg tggggaacat cacacgctgg ggcctgtcgt ggggtggggg 142320gctgggggag gaatagcatt aggagatata cctaatataa atgacgagtt aatgggtgca 142380gcacaccaac atggtacatg tatacatatg taacaaagct gcacgttgtg cacatgtacc 142440ctagaactta aagtataata aatttaaaaa aaataaatat atgtggaaaa tattaatagg 142500tcaaaattca aattgttcat ttaatcagaa gagtagttta gtcaaatcca agggttagac 142560aacagaaatc ttttttgtca agtgcattct ttgtgactga tttcattttc ttcctggttt 142620acacaggaag atttcagaaa caaatgtgga tccgtgacag atggtatcta gaagttttta 142680gtttggttga attgacagta ttttattgag taaaagatac taatttttgt aagaagaaaa 142740attcaatttt gataagtatg tttaagatta agagctattg gccaggcgct gtggctcatg 142800cctgtaatcc tagcactttg ggaagctgga gcaggtgggt cacgaggtca agagattgag 142860accatcctgg ccaacatggt gaaaccctgt ctctactaaa ttagccaggc gtggtggcac 142920atgcctgtgc acccgcctcc gggtttaagc gatcctactg cctcaggctc ctgagtagct 142980gggattacag gcgccatggc taatttttgc atttttagta gagacagggt ttcactacat 143040tggccaggct ggtctggtct caaactcctg acctcaggtg atctgcccgc cttagcctcc 143100caaagtgctg ggattacagg catgattcac catgtctggc catttatctt attttctttt 143160tttttttttt ttttgtttga gacggagtct tgctgtgtcg cccagagctg gagtgcaatg 143220gtgcgatctc agctcactgc aacctctgcc tcctgggttc aagcaattct cctgcctcag 143280tcttccaagt agctgggatt acaggcgcgt gccaccacat ctagctaatt tttgtatttt 143340tagtagagac agggtttcac catgttggcc aggctggtct cggaactcct gacctcgtaa 143400tctgcccacc tcggcctccc aaagtgctga gattacaagt gtgagccact gtgcccagcc 143460atcttatttt ctttcttttt ttttgtcggg tgggaggggg acagagtcta gctctgtcgc 143520caggcttggc tcactgcaac ctctgccccc caggttctag caattattct gcctcagcct 143580cccaagtagc tgggattata ggcacctgcc accacgcctg gctaattttt tgttattttt 143640agtagagatg gggttttgct atgttgacca tgctggcctc aagtgatccg cccaccttgg 143700cctcccaaag tactgggctt acaggcgtga gcttgtattg ggtaaaagaa caatattggg 143760ggctgcatgg tggttcatac ctgtaatctg agcactttgt gagactgaga tggaaggagt 143820gttggagccc aggagggtga ggctgcggct gcagtgaatt gtgatcacgc cattgcactt 143880ccacctaggt aatggagcaa gaccatgtct ctaaaaaaca aaacacaatt tttttaagga 143940atactgggaa gaggtcagtg gtggttttag aacagaggaa gtgccagatg acctttgtga 144000ggcattggcc aggaagaact ctacagtgtc tttaggtagc ttctgtccat aaggataatg 144060gggtctcctc cccagtatta atagaaaatc tctgagctgt ttttttttgt ttgtttgttt 144120tgtttttttt tcctgagatg gagtctctct ctgtcggcca ggctggagtg ctgtggcgcg 144180atcttggctc actgcaagct ctgcctccca ggttcacacc attctcctgc ctcagcctcc 144240caagtagctg ggactacagg tgtccaccac cacgcccagc taattttttg ttatttttag 144300tagagatggg gtttcaccat gtcagccagg atggtctcga tctcctgacc tcgtgatccg 144360ctcgcctctg ccttgcaaag tgctggagtt acaggcgtga gccaccgtgc ctggcctggt 144420ttttttgttg ttgttattta tttatttatt tatttatttt ttgagacaga ctctcgctct 144480gtcgcccggg ctggagtgta gtggcacgat gtcggctcac tgcaagctct gcctgccagg 144540ttcaagccat tctcctgcct cagcctcctg agtagcaggg accacaggcg ctcgccacca 144600cgcccggcta attttttgta tttttagaag agacggggtt tcaccgcatt agccaggatg 144660gtctcgatct cctgatgtcg tgatccgccc acctcggcct cccaaagtgc tgggattaca 144720ggtgtgagcc accgtgcctg gcctgatttt tttttttttt taatctggtc tcatacctct 144780gacagctcat gaagaagtgc tcctgcttca tatgtatatg tgttagcata gtgttaacat 144840agcataggtg ttcggtgttt gcagtttctg tttgttttat atgaattaag gtgtattatg 144900agcagttgaa gatatatagg aaattttttc ccaaaccact atctctgctc gttctattca 144960ttcagtctgt ttatgttatt ccttcattca ttcattttat agaacagtgg agtgcctact 145020gtatgcatct attgttctgg gtcctgggga agaaaacaaa gttcctgctt tcatggaact 145080tacattatat tggcggagac agtaacagac aaacaaatgt agcctgtgta catgtgttac 145140atgaaaagca gggtaggggg ctgggagaga gtagtaggga gtgctatttt cgaggtggtt 145200gtcaggaaag gcctcactga ggaggtggca ttttgagtag acctgagcgc agcgggggcg 145260taagcccagg cagcatgtgg aggaagagtg ttcttggtga aaggaacaag gatagaggcc 145320cgaagctaga gagctcagca tgatcaagga acagcaagcc ccgtgtggct ggaatggagt 145380gagcaaagga atgagcagta gaaggtgagt gagttgggag gtcaccagag accatggcaa 145440ggacttgaaa gtgtcaggga cacattggaa gttggagcag ggaaatgatg ggatttatgt 145500tttgtttttg ttttatgttt agtgttttta agggattgct ctatcagcta tttggaaaat 145560ttagtgtagg gcttcaagaa gagaagcaga gaaacaacat tcttgccata gtcatagtct 145620aagtaaggga tgatggtggt gtggattagg ctggtagtgg aagaccagtc cagttcgggt 145680tgtatttgaa ggtagaggca aaaagattat atttctacca gcaagcccat ctatgaagtt 145740acttgtatta ttaatttaat tgagacatgc ccacataaac taataaatag gaatttctgc 145800agtttggtta aacacccctg tatatcctgg ttcttctttt agttgtccag atgtctcttt 145860aagtcaagta ttttttggtg gtgtaggagc ctagagattg aatttattca cccaaaaggc 145920atttgagtga ttactatgtg ccaggcacta tgctgaatgc caaggatgta aataagaggg 145980cgtagtctca gtctgtttta ctccagcttg gttccttttt aatgaccctg acttgttaag 146040catatcagtt atcctacaga atgtttaatc ttctgtactt tcctggttgt gttatttagc 146100ttatttctct ttccttgaca tttcttgtaa actggaagtt acacctatag tcttgatgat 146160tcgtgttaca cattttagat tagaacacat catgtgttgt atatggtgtt tttgaaagcc 146220tctctgtata ttggtctgta cattaaaatg ttgcctgaat ggatacacat aaaatttaac 146280agtgattaca ttagagatga gaagaaagag gtgcctttta cttttcaata taccttttcc 146340tctgcttttt gaactttctt gccctatgca tacgttattg cttaatcatc cacctcatct 146400cttcccctgt ggctttctgt tgcatttgga atgaaatcta gcctctttgc tgttacctgt 146460ggatgtccct tgctggcctc tatcacctta ctttgaacca ctcctttcat ggactgagct 146520ctcattggac tatcttttat tcttttgctg aagtttcttc actttgagtg cctctgcagt 146580tgctatttca tggctgtggc aagccctgcc atggctttca tgcaaggatg gttcctcctt 146640ctcatctcaa tattatctct tcagagaggg accttcccaa ctccgatgat ctaaaatcct 146700ttgtatatac cactcactac cacttctttc ttttcttttc cttttatctt tttttttttt 146760tttttttttt gagatagggt cttgctctgt tgcccaggct ggaatcacga ctcactgcag 146820cctcatcttc ttgggctcaa atgatcctct cacctcagcc tctcgagtag ctggaactgc 146880aggcacacac caccatactt ggcttattat tttacttttt gtagagacag ggtttcacca 146940aggctggtct caagctcctg ccgcaagcaa tccacatctc tcagcctccc aaagtattgg 147000gattatagga gtgagccact actcctggcc tattttctta ttcactgtct aaaattatct 147060tgttcattta tttacatact tgtttatagc ttatttctca gctggacatg gtgcctcaca 147120cctgtaatct caatactttg ggaggctggg ttggagaatt ggttgagccc aggacttcaa 147180gaccagcctg ggcaacaaag tgagaccctg tctataaaaa attgtttaaa aattagctgg 147240gcatggtggc acatgcctgt ggtcccagct acttgggagg cagaggtggg agaatcgctt 147300gggcccagga ggttgaggcg acggtgagcc atgattgtgc cactgcactc tagcctagtg 147360acagagtgag accatgtgtc taaaaagtaa ataaaaatag tttctctttc atgactagaa 147420tattacctct atgtgggcag ggagtttgtc tatactattt ggcactatat ttcctgattc 147480tgaaattatg cctagcacat ggtaagtact ccttaaatat ttattgactg aattatttaa 147540tacttaagaa tttcatttgg gattatctga gtggtaagat tacggattat atttatgtaa 147600gaaaaaatca ttttttaaac ttggttgccc tttgccacac tgacatagac actaagtttt 147660cttagccaga ttacttccga ggatactcac agaggccatt ctcttctcaa tccccaaata 147720attgatattt cttagcactt tcaagctaat gcaattctta gatgatgtat ctgtgtatat 147780catatcctca ttctacaaat gtagaaattg aagtctgggc acagtggctc tcacctgtaa 147840tctcagcagt ttgggaggcc aaggcgagcg gatcactgag gacaagagtt aagaccagcc 147900tggccaacat ggtaaagcct tgcctctatt aaaaatacaa caattagggc cgggcgtggt 147960ggctcacgcc tataatccca gcacgttggg aggccaaggc aggcagatca cgaggtcagg 148020agttcgagac catcctggct aacacagtga aaccccatct ctactaaaaa tacaaaaaat 148080tagccaggca tggtggcacg cgcttgtagt cccagctatc gggaggctga ggcaggtgaa 148140tcccttgaac ccgggaggcg gaggttgcaa tgagctgaga ttgcaccgct gaactccagc 148200ctggtcaaca gagggagact ctgtctcaaa aaaaaaaaaa aaaaacaatt agccaggcgt 148260ggtggcgggt acgagtacct gtaatcccag ctactaggga ggctgaggga ggagaatcac 148320ttaaacccag gaggtggagt ttgcagcggg ctgataatgc accactacat tccagcctgg 148380gcaacagagt gagactctgt cttaaaaaaa aaaaaaagaa agaaagaaat tgaggaatgt 148440ggagattgtg gtctgtgatt tgttaggaat cacacagcag gttagtagca actacagggc 148500tttggttcag aataccacct tgacaatggt ttgtttacag ttcggctccc cttcctctgc 148560ctttctctcc ttccttattg agggcagctg gaaagaattt tcatcattta ctagcctata 148620gctttaattt gagttttgaa accttgataa tagagcacag aggaaaagac tgagttttct 148680ttttttgaga cagtcttgct ctatggccca ggctggagtg cagtgacacc atctcagctg 148740gttgcaacct ctgcctccca ggttcaagca attctgcctc agcctctcga gtagctgaga 148800ttacaggcac gtgtcaccac gcccagctaa ttttctgttt ttgtttcgtt ttgttttttt 148860ctgagatgga gtcttgctct gtcacccagg ctggagtgca gtggtgcgat gttggctcac 148920tcaaacctct gtctcctggg ttcaagcaat tcttctgcct cagcctcccc agtagctggg 148980actacaggta cgtgccacca tccctagttc atttttgtat gtttagtaga gatggggttt 149040cactatgttg accaggctgg tctcgaactc ctgatctcag gtgatctact cgtctcagtt 149100tcccaaagtg ctgggattat tggcacacgc ctatttttgt atttttagta gagacggggt 149160ttcaccatgt tggttagact ggtctcaaac ttctgacctc aagtgatttg cccgccccag 149220cctcccaaag tgctgggatt acaggcgtga gccaccgtgc ccagccaaga ttgagttttg 149280aaaagagcct tctgagatta tgagaagggc aagcaagata acttaagaag ttacattaaa 149340atcatctaag agacagtgta acaagaagga attgtaaaat gatgttatga gcacgtgccc 149400aatgtagtgg caatcccttg tgcttcgata cattggtggg agacaaaact gtacttaaat 149460tgataaatcc cttacatgtc attttaagga gcttagactg actcccatca tgtagacatc 149520agagatttct tttttttttt tttttttttt tttttttttt tttgtgacag agttttgctc 149580ttgttgccga ggctggagtg caatggcgtg atctcggctc accacaacct ccacctccca 149640ggttcaagca attctcctgc ctcagcctcc cgagtagctg ggattacagc catgcaccac 149700cacgcctggc taattttgta tttttagtag agacggggtt tctccatgtt gtggctggtc 149760tcgaactcct gacctcaggt gatcctcccg cctcagccac ccaaagttct gaaattacag 149820gcgtgagcca ccgcgcccag cccagagatt tctaaacaga gttctaacca gatgcttttc 149880cctgtcagta gaatgagaat gaattggagg tgggagagac tggcatgagg gacaccagtc 149940agccagtgga attagctggt aatgttgata ggagaagaaa aagattcaaa gttaggtagt 150000ggtagcaaga attagaggga aggtcggatt tatgatatgt ccaaggttga attctaaggt 150060gaaatttggt ggcagatttc atgtgtaaat tgggaaggta gattgagttt ttttaacatg 150120ggttttctaa catgtcaata gagtgactct gcaggggggc ctgacgagag aacagtgcat 150180ggggtgattc aacagccagt tgagccttca tgcagagcat ttaacactgt gactctgtag 150240actctggttg gcagtaaaat ttcattaaac caatatttaa acccttaggt aataataaaa 150300attgagggaa aaggatccag gttttgtatt ttttatgaat tcagttattg aattaaacag 150360gaccttgcct caagaaataa tctaccaaca attaacttgt tttaaagcaa agttaggaag 150420tgagcatgtt caaattatta aataaaaaag taagctgtgt atttcattca tagaaataga 150480ggctggccta cttcggatga ttctcagcat gtgattacag atgtgggctt atacatccta 150540gggagttaag gcgtactctg gcttggatag agtagagctc tttgaaactc ttctctcacc 150600cagctagttt atatagacta gagaactaga atgtagcagc atactctgtc ttagaagccc 150660ttttatatag gagctggtct ggaaggtttg aaaacataac aaatgtgttg gtgtctccca 150720atgtattgct agattcttac ccaagagcat tatcctggtt agggtttggt ttggttttgt 150780tttgtttttt aatgtttgcc acaaactaac actagatgtt agttctttca tcaagtgagg 150840agagtagaag aaaagtccag aactctgaaa caccttttca aaagtttttc aagccatgat 150900gtttgcaagt taaatgctct gttatgtaag caatataatc agtttttatt aatgtaacat 150960tccttagtgt tttggggtat cacacaaaaa agaatatcca tatctggaag caacagcttt 151020taaataagag cattgtggtg gtggtggtga tagtggtttt tttttttttt tttgagttgg 151080agtctcgctc tgttgcccag gttggagtgc agtggcacga tctcagctcg cttcaacctc 151140tgctcccagg ttcaagcaat tcttctgcct cagcctcctg agtagctggg attataggca 151200cctgctacca tgcctggctg atttttatta ttttagtaga gacaggtttc accatgttgg 151260ccaggctggt cttgaactct taacctcagg tgaatcaccc acctcggcct cccaaagtgc 151320tggaattaca ggcatgaacc accatggcca gccaaataag agcattttta atgtaaaatt 151380atgcatgaaa tgtacattca attttgtctt tgtttactag gatccatgtt ctcacaagct 151440atgaagaaat gggtgcaagg aaatactgat gaggtaaatc ctacctttag gataaaaaga 151500tttctgttta taagtgccac cctcatgtaa gtgaggttta aaattttcct tttctttagg 151560tcccatgttt aagcagcatg gcacatttat gttctcttac ccagaatgta ccaagaaagg 151620gtggtccctt cttaacatct aacaattgcc tggtagtagc agtgaaggta tcttcagtca 151680gaggctagga ccactgaagg atatacatgc attcaagttt ccatcagcca gcaggcatca 151740gtaatcagtg tgtagatcaa aagctcaaat gtttccttcc ccactggcag ttttacttca 151800agtagtggag gcttgctttt ttaatagtta attaagtaca ttgagagatg ggaggtgaaa 151860aaaggaaaat gttttatttt gaccatctaa tatgaaagta gttcggtgtt aggtatccag 151920tagttgacac tggaagacag ggaatgacat gttaatattc atagccagag ggtggcccag 151980gttttttcgt acatgggaat gaaattctta tccaaataag tagaaattat gtgcgtaagc 152040catttgttaa gagcactgag tatgtgcatc tcgatccatc taatgaataa ccattatcac 152100cagtttaaat tattttcttt aggcccagga agagctagct tggaagattg ctaaaatgat 152160agtcagtgac attatgcagc aggctcagta tgatcaaccg ttagagaaat ctacaaaggt 152220aaggatgact tcgttttgtg taaactaaaa agtattattt tccaggtgta aaaataaaaa 152280agaacataag gggtttcttt gcctttgaag gattaactgc tgtggggatt accttcttat 152340cataagcaac tagaaaattg acaaactaaa tgaaacaact gtttgcatat attggacaat 152400gggcaataca gggaaaccat ggaaaccaaa cagagcccag tagtcttgct gaacgaaaga 152460gttaaatatc aaagttcagg ccaggtgcag tggctcacgc ctgtaatccc agcactttgg 152520gaggccaagg cgggtgaatc acttgaggtc aggagttcaa gaccagcctg gccaacatgg 152580tgaaaccctg tcttagccgg gtgtggtggc aggcacctgt aatcccaact atttgggagg 152640ctgaggcagg agaatcgctt gaaccaggga ggcggaggtt gcagtgagcc gagatcacac 152700cactgcactc cagcctgggc gacgagcgaa accccatttc aaaaaaaaaa tcaaagttca 152760gagagctcaa tttgagtaga agttgtagga taaggtagca gaaaagagga agctgcccag 152820aaagaaagcc gtagagatat ttagagagat tcccatggat ccttggccta ggagtgatct 152880gtatatgtgt ggggtgaaaa cgcatgtgtc caggtagaga accccccaga aattagtagg 152940ctgaatgatt gctggaacat agggctaaga aaagttcatg gccagaagga tctggccaga 153000gtagagagac ttagtaatac acaaggcatt gggtagtgtc ttcacagagg ttatgcctta 153060ctactgaaga taaattagtc ctagagtaca agcacctgaa ccaagtttca aagcaaattt 153120ttaaagggtc aaattaccta acaactgcat gccaaaacaa aggcctaacc ctctttacag 153180taacacaaca aaattcagca cttcacagtg taaagttaga atgtctgacg tccaggctgg 153240gcgcagtggc tcatgcctgt aatcccagca ctttgggagg ccgaggcagg tagatgacct 153300gaggtcagga gttcaagacc agcctggcta acatggtgca accccgtctc tattaaaaat 153360acaaaaactt agccaggcat ggtggccggc acctgtgatc ccggctactt gggaggctga 153420ggcaggagaa ttgcctgaac ccaggaggtg aaggttgcag tgagccgaga tcgcaccact 153480gcactctggt ctgggcaaaa agagcaaaac tcaggctcaa aaaaaaaaaa gaatgtctga 153540cgtcaatcac aaattaccaa gcatgacatg aagttgacct ataaccagga gaaaactcaa 153600tctatagaaa cagacccaga tgtgagaaag atgatgaatt tagcagacaa agaccatcaa 153660gtggctattt taaatattaa aaatatgttc aagtggccag gtgcagtggc tcatgcctgt 153720aatcccagca ctttgggagg ccaaggtggg taggagttca agaccagctt ggccaatatg 153780gtgaaacccc ttctctacta aaaatacaaa aaaattagct gggcatggtg gcaggtgcct 153840atagtcccag ctatatggga ggctgaggca caagaatcac ttgaacccgg gaggtggagg 153900ttgaggttgc agtaagccga gattgtgcca cttgtactcc agcctggaca acagagtgag 153960actctgtctc aaaaaaaaaa aaaaaaaagt taaagaaaac aagagtataa tgagaaaaat 154020gcaaaatagt tttaaaagaa ccaaatggaa tttcttaaaa taaaaaatac cagaaatggg 154080ggccgggcgt ggtagctcac gtctataatc ccagcacttt gtgggggctg aggcaggcag 154140atcacctgag atcggtagtt caaggccagc ctgaccaaca tggagaaacc tcatctctac 154200taaaaataca aaattagctg ggcgtggtgg cgcattgcct gtaatcccag ctacttggga 154260ggctgaggca ggagaattgc ttgaacccgg gaggcagagg ttgcggtgag ctgagattgc 154320accagtgcac tccagcttgg gccacaagag tgaaactccg tctcaaaaaa aaaacaaaaa 154380aaaacagtag actcgaagaa ctagctgagt ttttctttac tttaggcagt aagtgtgacc 154440ttttgcaggt gactacttta gttcctcatg tcctcattag tagatcagag aaattcgaca 154500ccaaaacccc aaaagaaaaa ccccttctaa tcctcattcc atgattttat gaatgcatga 154560agtcctaggc ctgcgaagga atactcattc tctttatcct gtgttgatac ctctctgctt 154620caacctccaa ctcgacattt gcctatagga tgtacttgga cattcagcat aaactacctc 154680acaccattac tgaattgctt catgtgcaca tgtcccatgc cacaataccg gggaccttgt 154740cttccgtgat atttgtccgc agtgctgtga ctacaggagg gagtcagtga atgtctgcat 154800gtgtgtcttt accatccctc ttgaatatgc tctagggtta attcctagaa gtagaattac 154860tctattgaaa attggcaata tttttcattc taatatctat tgccaacatg ggaaagcaag 154920tctggatgcc agtccttgtt atatgcccct tgggtaagtt acgtaacctc tttaagcttc 154980tgttcactca tattttaaca aggaaaatta caatatttta cctcacaaaa ttgtagtcag 155040cttctggctg tcttaaactc tggtatatag taaacactaa gtgttggtgt ccatccttaa 155100tttgtaataa taggtcactt gttagagaaa tgcaccttac cattttcttt tcttttcttt 155160tttcagttat gactcaaaac ttgagataaa ggaaatctgc ttgtgaaaaa taagagaact 155220tttttccctt ggttggattc ttcaacacag ccaatgaaaa cagcactata tttctgatct 155280gtcactgttg tttccaggag agaatgggag acaatcctag acttccacca taatgcagtt 155340acctgtaggc ataattgatg cacatgatgt tcacacagtg agagtcttaa agatacaaaa 155400tggtattgtt tacattacta gaaaattatt agttttccaa tggcaataac ccatttatga 155460gagtgtttta gcctactgga atagacaggg accacatcct ctgggaagca gataagcata 155520gaactgatac ttgatgcaca ctcgtagtgg taactcatcc ctaatcagca ttgtaaagca 155580ggtgccagag gtggtttgct ttgtccttcc aaagcaggtg agtcagcccc accgagagcc 155640aggcagcttt gagtggcagc gtggtgctag cagcttcagc ggaacagggt gagagttaat 155700tatgcagtct tcttgacagc ggcattaatt tggaaggaaa ctgacaagtc atgggtcaag 155760tttcagtgac ttcctccttc ctctgatggc agtatatagt tttcacattt taattcctcc 155820tcctgagatg cactatactt aaaaccattc tctcccctgc taacagaagg gtgtgaatct 155880ggtttacttt gagcattagg atttgcccct ttggaattct gcactccagt tacttaactt 155940tcccttcaga atacatgtgg aaagaaagaa agaaatagcg atgactccac ttttgcccct 156000gtggcacctt gaacaaagca gttcttccca aattatactt tttttttttt taaataaggt 156060gagcaggatg actggggaga gagaaacatt tgactttgac tgcctccccc attctttgct 156120gtgagctgga aagtgtgcag ttggtcgtct ttcttctcct ttctttagga tagtaagaga 156180ctcactcact gcacttctgc tcagttggct tctgcatcgg gatcacacag ccatcagcag 156240gactgcccag ttggtgagca cactccattg accacgtggc gccagcgctt cctcaatgca 156300catgattgag aggaaagaaa gttctcttag atgttactgc ttttgctcag actttgcaaa 156360aaaaaaaata tatatatata tgtataaata tataattatt aatcactttt gtccttgaga 156420aagtcttgaa tgaacagaga atttattcca ttgcaatatt tgattgtata gaggcacact 156480gtttcatcga cagaagaagc aaaaaggctt tgtgtaagtt tttggtacta tgtaccacct 156540ctgttattct tttaaagctg aagtattcat gtacttaaac catattatat ttaattgtgt 156600ttgattttaa aatatatata tatgaattct atttaaaatt gtgtcaactt tctgctttca 156660gggcatttat ggctcttctg ttgaaatata ttgatctttc caaatatttt catttgcttt 156720ctaaaaaccc agaacatgag ccactactgg actttgcctt gtgtttgaag tgtatggcat 156780aaacccaagg tttttattag tcatctatgc tgtgattaat tcattttgtt cttttaacaa 156840aatatttcca tccacttcac attgcttcaa tctttaacag aaaagcaata taaaggttat 156900agaataaaat gtggttttgg gcaactcttg ctgcctctgc atgttttgga ataacaattt 156960ctacaagact ctaggctgtt taaactagtg ctttcagtta agataaattc taatcatttc 157020tttgtatata cattttgtgc ttctgagcta gagatgccaa gtagttgtaa actgcttata 157080aagagaatag cagcaaattt gagactcggc tacttttttc tgccccacct gctttgagac 157140acagaagcgg agtgtggccc gaaattatta gccagattta atatttgatc taaagtaggt 157200ccttgtactc attttaaagt tggaatttga ttcctccaac attgagcacc caccatgttc 157260caggctctgt gcattgtgcc cacaaaataa gattccctgg tggagttttt atgggttcaa 157320ataatcagtt gaacaccctt catctttatc atgttgttga cattgacaca aattgtttaa 157380aaagaaaaga tattagagag aaagtggtac ctttgtaact tgatgtgtct tcatcattcg 157440gtaagatttg atgaaagtaa aaagcaaatg tcagccaaat ccagtgaaca gcaataaaac 157500agggagtaac tttttataac tttttctact tggatttcaa cattcagtag agcttttcga 157560aatgtaagta gtttacagta ctggaggttt gactagttca gtaggaattt ggaggggaag 157620gtcattctga attgtaacaa agtacaaact tctttgctgt tttatttaag tactgagagc 157680taagcacctg atgaagtgac tgacctctct ccagtgacag tgtttgggta cctgcctgac 157740ttcaggagtg gggtttatgt ttctacacag tgaccttttc tctcgccctc tcctccctct 157800tgcccacaca ccagttgatt ggacctgggt tgaactcctg atccagacag gcccaagaca 157860gttcttaatg ttaagaattt tggggccggg cacggtggct catgcctgta attgcaacac 157920tttgggaggc cgagacaggc ggatcacttg aggtcagggg ttcgaggcca gcctggccaa 157980catggtgaaa ccctgtcttt actaaaaata caaaaattag ctgggcatgg tggcgcacgc 158040ctgtaatccc agctacgtgg gtggctgaga caggggaatc gcttgaacct ggaggcggag 158100gttgtgcaat gagccgagac cgtgtcactg cattccagcc tgggtgacag agggagactc 158160tgtctccaaa aataaaaata agaaaaagaa ttttgggcta ggtgcagtgg ctcacgcctg 158220taattacagc attttggaag gcccaagatg ggcagatcac ttgaggacag gagttcgaga 158280ccagcctgga caacatggtg aaactccatc tctactaaaa agacaaaagt tagccagatg 158340tggtgatggg cacctataat cctagctcct cgggaggctg gggcaggaga atcacttgaa 158400cccaggaagc agagattgca gtgagccaag atcacatctc tgcactccag cctgggcaac 158460agagcaagac tctgtctcaa aaaaaaaaga atttggccag gcgcagtggt tcacgcctgt 158520aatcccagca ctttgggagg ccaaggcagg cagatcacga ggtcaggaga tcgagattgt 158580cctggctaac atggtgaaac cctgtctcta ctaaaaatac aaaacattag ccgggtgtgg 158640tggtgggcac ctgtagtccc agctactagg gaggctgagg cagaggaagg atgtgaaccc 158700aggaggcgga gcttgcagta agccaagatc gtgccactgc actacagtct gggcgacaga 158760gtgagactcc gtctcaaaaa aaaaaagaat tttggccggg tgcggtggca catgcctgta 158820gtcccagcac tttgggagac caaagtgggc ggattacctg aggtcaggag ttcaagacca 158880gtccggccaa tatggcgaaa ccctgtctct tactaaaaaa aatacaaaaa ttagccaggt 158940gtggtggcgg gcacctgggg aggctgaggc agggagaaat gcttgaaccg gggaggcaga 159000ggttgcagta agccaagatc gtgccactgc actccagagc aagactcttt ctcaaaaaaa 159060aaaaaaaaag aattttgcat ggggaaggag agatactgtt caccatctgg aatggtgctt 159120ggatgtggca cttacaaaat caggagccag cactgcatgg acaaacagaa gcatgtgggc 159180ctgagatagc aggtaccttg ataaccctga agacatcctt ggtttctgca tctattcctg 159240catccttgca ttggactaca ttaatctgtc agttatcctt ataatgattt ttgatttttt 159300ttttttgaga tggagtttcg ctcttgttgc ccaggctgga gtgcaatggc acgatctcgg 159360ctcaccacaa cctccacctc ccaggttcaa gtgattctgc tgcctcagcc tcctgagtaa 159420ctgggattac aggcatgcgc caccacacct ggctaatttt gtatttttag tagagacggg 159480gtttctccat gttggtcagg ctggtctcga actcccaacc tcaggtgatc accctgtctc 159540ggcctcccaa agtgctggga ttacaggcgt aagccatggt acccggtctg ttttttgatt 159600ttttgaaacc agtctgaagt gagttttttt aattacgtga aaggagtttg gctaaaatac 159660tgccatactg ccctaatgcc taatgattat gtattctcag catgtctgca aagtactgct 159720gatttctgga gaataatttt tctttagtaa acttcactta agtcgtcatg tgtattctct 159780caaaatggta tcctaaccta atggagctaa aagacacccc ttgtttttat aacaagcagt 159840tactgaggcc caggaagggg agaagtccct ggcttgtgag atgatcacca ttagaactca 159900ggcctgggcc agtgcctttt catgcttctc agatccttcc aaagaataat gaagattata 159960accgctttta gcaattgtaa taaacccaga aatagaaagc tttttggtta gagtactggt 160020agaagtttgg cgggagagat aatttttaca aaatttgtaa atacctgcca attctatata 160080ctaggcaagg tctctggcct tgtaaaaccc ctcaaggtta caactttggt ggcccacact 160140aatagttacc cactgaggcc ctctccgggt gaacattgag cactagagga agcccctctg 160200cttgggcagg actgggcgtg gtgcagagta ggagcggtga tactgtggat tctgggcagg 160260tggagatggc cagtgatgtc caataaagga cactggaggg agcagtgtga gtaaaggccc 160320tgagggcatt catgttcagg gagggttgct gcccactggc ttgcttggca cacaggagag 160380tgggtattcc tgccttagta actttatgta aacaagtatt tcctcagtct gttcctctca 160440aactgcctgc tctggcacat tcagaatgtc acagaactca cctggatgca ttcagcccct 160500tgcctaaagg tgacagtgca tctccttccc caccccaccc ctcataccac tgaagcacct 160560gtcagactgg cccagtctgt gggcaaggag cctagagagg gcttagtttc agcttgaaag 160620gagctgggat ttaccaagaa gcaaatgaga gacgaggatt gcaacaactg tgccatttcc 160680ccagcttcag ctgactcctg tatattgact gtgccttcag actcatccgt aagtgacccc 160740aggctggcct ctcccacatc acagtaagaa ttccacacac catacaactt ggaaagaggc 160800tccagctgaa ggaagcccca cacttctttc aagtttttct tagtcttctc ttcttggcaa 160860agagtacctt ttgtttcttc taattatgta actattggtt tagtaaatat tcacccattc 160920agtcaccctg taagtggcag gcactgttta cagggacaca ggaaggaata aaaacttgca 160980ggcaccttgg agcttgcatt ctattgaaga ggtaatggaa gttgggatag cagctaaact 161040atgctggtat tggccaggcg cagtggctca cacctgtaat cccagcactt tggaggccaa 161100ggtgggcaga tcatgaagtc aggagatcga gaccatcctg gctaacatgg tgaaaccccg 161160tctctactaa aagtaaaaaa aaaaattagc caggtgtggt ggcgggcgcc tgtagtccca 161220gctacttggg aggctgaggc aggagaatgg tgtgaaccca ggaggcgaag attgcagtga 161280gccgagatgg caccactgca ctccagcctg ggtgacagag cgagactctg tctcagaaaa 161340aaaaaatatg ctggtagttt tgattcaaga tggcctttgg agcccatgat ttaggtctcg 161400tacccaccaa ggtctactgg aaaacatcag gctctcctgc tatagaccca tagggagagc 161460tgcagccgag agggggagct gaagagaagt gccccttctg tgtcctgtca gcctcatcct 161520tccgcaagga ccagttgctg tgccactcca ttcacttgct gcaagactgg aggtttttcc 161580tcaggtgttg agcacctggt ttacaagatg tcagcatctt gatgcctgag accatcaagg 161640caagtctctg aacagggctt accttagagt aaggcttaga agaggccgta aagtcagtct 161700cagctccgtg gctctgcaga gctttgggac atgtgaattc ttaaaaacaa gactattgta 161760cagttactat atgcatgcag tataaaatta taaccttgga aaatcctagc tagctgttga 161820gctaattcca taaagtaatc agctcctgag ttctgcagtg gtaataataa tcagcataat 161880gagtaaacac tgtgtgtgcc aggcagcgtc tcatttgatc cttgtgataa tcttgtaagt 161940actgattttc tcccttcttt aaacaaagtt tttttttttt ttttagagag ggtctcacta 162000tgttgcccag gctagtcttg aattc 162025 <210> SEQ ID NO 36 <211> LENGTH:162025 <212> TYPE: DNA <213> ORGANISM: Homo Sapien <220> FEATURE: <221>NAME/KEY: mutation <222> LOCATION: 156,277 <223> OTHER INFORMATION:Nucleotide Base Change: T to C <400> SEQUENCE: 36 gaattcctat ttcaaaagaaacaaatgggc caagtatggt ggctcatacc tgtaatccca 60 gcactttggg aggccgaggtgagtgggtca cttgaggtca ggagttccag gccagtctgg 120 ccaacatggt gaaacactgtctctactaaa aatacaaaaa ttagccgggc gtggtggcgg 180 gcacctgtaa tcccagctactcaggaggct gaggcaggag aattgcttga acctgggaga 240 tggaggttgc agtgagccgagatcgcgcca ctgctctcca gcctgggtgg cagagtgaga 300 ctctgtctca aaaagaaacaaagaaataaa tgaaacaatt ttgttcacat atatttcaca 360 aatttgaaat gttaaaggtattatggtcac tgatatcctg tttcattctt tatataatca 420 ttaagtttga aatgtatacttgcactacta acacagtagt taatcttagt cctacaagtt 480 actgctttta cacaatatattttcgtaata tgtatgcact ggtgtttatg tacgtgttta 540 tgtttatatc tgttaaaattagcagtttcc atctttttct attttgtacc atcacatcag 600 ttcagaagga ttgacagagcaaaatgattt gatgaagtat aaaagtcaca tggtgagtgg 660 cataaataca actctgaacaattaggaggc tcactattga ctggaactaa actgcaagcc 720 agaaagacac atatcctatatgtcaagaga tgtaccaccc aggcagttaa agaagggaag 780 tacacataga aagcacaatggtgaataatt aaaaaattgg aatttatcag acactggatt 840 catttgctcc taaagtcagagtcctctatt gtttttttgt ttttgtgggt ttctttttaa 900 atttttttat tttttgtagagtcggagtct cactgtgtta cccgggctgg tctagaactc 960 ctggcctcaa acaaacctcctgcctcagct tcccaaagca ttgggattac agacatgagc 1020 cactgagccc agcccagacgctttagcatt tatgaagctt ctgaaatagt tgtagaaacc 1080 gcataagctt tccatgtcactttcaaagtt tgatggtctc tttagtaaac caaccaagtt 1140 attcctcaag ggcaaaataacatttctcag tgcaaaactg atgcacttca ttaccaaaag 1200 gaaaagacca caactatagaggcgtcattg aaagctgcac tcttcagagg ccaaaaaaaa 1260 aggtacaaac acatactaatggaacattct ttagaagagc cccaaagtta atgataaaca 1320 ttttcatcaa agagaaaagagaacaaggtg ttagcaaatt cctctatcaa ataacactaa 1380 acatcaagga acatcaatggcatgccatgt ggaagaggaa gtgctagctc atgtacaaac 1440 cagtagataa tttcaacttgctgccgaatg aaacctcttt gcaaggtatg aatcagcact 1500 tctcatgttt gttttgctttgttttgtttt gtttttagag acaggccctt gctctgtcac 1560 acaggctgga gtgcagtggcacgatcagag ctcactgcaa cctgaaactc ctgggctcaa 1620 gggatcctcc tgccttagcctcccaagtag ctgggactac aggcccacca tgcccagcta 1680 attttttaaa ttttctatagagatgggatc tcactagcac ctttcatgtt tgatgttcat 1740 atacaacgac caaggtacaatgtggaaaag ggtctcaggg atctaaagtg aaggaggacc 1800 agaaagaaaa ggggttgctacatagagtag aagaagttgc acttcatgcc agtctacaac 1860 actgctgttt tcctcagagcagagttgatg atctaaatca ggggtcccca acccccagtt 1920 catagcctgt taggaaccgggccacacagc aggaggtgag caataggcaa gcgagcatta 1980 ccacctgggc ttcacctcccgtcagatcag tgatgtcatt agattctcat aggaccatga 2040 accctattgt gaactgagcatgcaagggat gtaggttttc cgctctttat gagactctaa 2100 tgccggaaga tctgtcactgtcttccatca ccctgagatg ggaacatcta gttgcaggaa 2160 aacaacctca gggctcccattgattctata ttacagtgag ttgtatcatt atttcattct 2220 atattacaat gtaataataatagaaataaa ggcacaatag gccaggcgtg gtggctcaca 2280 cctgtaatcc cagcacttcgggaggccaag gcaggcggat cacgaggtca ggagatcgag 2340 accatcctgg ctaaaacggtgaaaccccgt ctactaaaaa ttcaaaaaaa aattagccgg 2400 gtgtggtggt gggcacctgtagtcccagct actcgagagg ctgaggcagg agaatggtgt 2460 gaacctggga ggcagagcttgaggtaagcc gagatcacgc cactgcactc cagcctgggc 2520 gacagagcga tactctgtctcaaaaaaaaa aaaaaaaaaa aaagaaataa agtgaacaat 2580 aaatgtaatg tggctgaatcattccaaaac aatcccccca ccccagttca cggaaaaatt 2640 ctcccacaaa accagtccctggtgccaaaa aggttgggga ccgctaatct aaataatcta 2700 atcttcattc aatgctaaaaaatgaataaa ctttttttta aatacacggt ctcactttgt 2760 tgcccaggct ggagtacggtggcatgatca cagctcactg tagcctcaat cacccaggcc 2820 ccagcgatcc tcccacctaaacttcctgag tagctgggac tacaggcacg caccaccatg 2880 cccagctaat ttttaaattttttatagaga tgggggtctc accatgttgc ccagactggt 2940 ctcaaaccct gggctcaagtgatcctccct caaactcctg gactcaagtg atcctccttc 3000 cttggcctcc caaagtgctgggattacaag catgagccac tgtacccagc tggataaaca 3060 ttttaagtcg cactacagtcatggacaatc aggcttttca acatgcagta tggacagtga 3120 gtcccagggt ctgcttttccatactgaaat acatgtgata ctaaggagaa aggtgctcgc 3180 aaggatattt aaaatgaagaatatttaaaa tgaggaaaaa actgtttctt catgactttg 3240 ataaggctga taaagaccatttctgtgatc tcaggtgatt cactcaagta gtatatttca 3300 gtaatcatta tctggaacagcctgaatctt aaccaaaata ccatgatttt ttaatgctgt 3360 tatgatacct tgatgatatgaccaaactgc aatgtaggca gctaaatctc cacgagtttg 3420 acttccccga gagttgacagttttcttcac aaattaaaga aatatatttt ttgatacatg 3480 attggcatat ttaaaaactacactgaaatg ctgcaaaatg atataaagaa acattttcca 3540 gaatcaaatg caatcaaagagtggattagg aatctactca ccattatcaa ctaaatagaa 3600 acacttggac tgggtgtggtggctcacatc tgtaatctca gcactttggg aggccaaggc 3660 aggtggattg cttgaggccaggagctcaag accagcctga gcaacatagc aaaactctgt 3720 ctctacaaaa aaaaaaaaaaattaaccagg catggtggca gatgcttgta atcccagcta 3780 ctctggaagc tgaagtaggaggactgcttg agcccaggag atcaagactg cagtgagccg 3840 tggtcatgct gcgccacagcctgagtgaca gagagagacc ctgtctcaaa aacaaaaaca 3900 aacaaaaaac acttaaccttcctgtttttt gctgttgttg ttgttgtttg tttgttttga 3960 gatggagtct cactctgttgcccaggctgg agtgcagtgg cgtgatcttg gctcactgca 4020 agctctgcct cccgggttcacgccattctc ctgcctcagc ctcccgagta gctgggacta 4080 taggcgcccg ccaccacgcccggctacttt tttgcatttt tagtagagat ggggtttcac 4140 cgtgttagcc aggatggtcttgatctcctg acctcgtgat ccacctgcct cggcctccca 4200 aagtgctggg attacaggcatgagccaccg cacccggcca acctttctgt tttttagttt 4260 gatatgcttg ttaactcagcagctgaaaga atgctgaaag tggccttcag taaaaaaatt 4320 tcactagaat ctctacatccatatttaatc tgaatgcata tccagattga tcagttagag 4380 caaaaacact catcatcattcctgatgacc tctaattctg gtttcggctt tctatttcaa 4440 tggaaacaga ataaggaaagaaatggaagg gctctggaaa tttgtcctgg gctatagata 4500 ctatcaaaga tcaccaacaataagatctct cctataaata taaaacaagt ataattaatt 4560 ttttaattat ttttttctcttcagaggatt ttatttcaag ataaaacata acttctaccc 4620 atactattga ttccaaaggttagaaaaagt gtttttcctc atcttatcct tcaaagaggt 4680 cacagcaatg caaacatctataaaatgcct ctgcataatt gtcagaagct atagtccaga 4740 aatcattgaa aatgcttttccattttaagc ttaggtgagg tgtcttagga aacctctatg 4800 acaacttact ctatttattgggaggtaaac tcccagactc tcccagggtc tcctgtattg 4860 atctcatttt ttaggcttcctaatcccttg aagcacaatc gaaaaagccc tggatctctt 4920 ttctgcacat atcatcgcggaattcattcg gcttccagca agctgacact ccatgataca 4980 agcggcctcg cccttctccggacgccagtc cttgctgcgg ttagctagga tgaggggttt 5040 gctgggcttc agtgcaggcttctgcgggtt cccaagccgc accaggtggc ctcacaggct 5100 ggatgtcacc attgcacactgagctcctgg caggctgtac caatttttta attatttaat 5160 atttattttt aaaattatggtgaatatttt ggtattctgc tctaaaatag gcccataaat 5220 gcacagcaga tatctcttggaacccacagc tttccactgg aagaactaag tatttttctt 5280 ttaaagatgc tactaagtctctgaaaagtc cagatcctct acctctttcc atcccaaact 5340 aagacttgga atttatgagagatctagcta acagaaatcc cagacacatc attggttctt 5400 cccagagtgc agtcctcctaaagaggctca gccctaagca ggcccctgca ccaggagggt 5460 gggtctgaga cccacatagcacttcccaag gtgcatgctc cagagaggca ctgaaacagc 5520 tgagcacaag cctgcaagcctggagaactc tcacagtcag aacggagggg gcccagtggg 5580 actaacataa agagaaaagggaacacagag aaatggatgg caccaacaac cagcaaagcc 5640 ttcatggcca atgaaagcatcagtgacggg gccagaaccc tcatccccaa agactcttca 5700 ctgcctttag tgaaaaacaatggctagaga gtgaagttat gatcatgtat agagaggtaa 5760 agttacattt ttatattctgactctgctaa tgtgaaattc cctatctgct agactaaaag 5820 tttcagacac cctgttcaaatatcccatta gttgctagag acttaaaatg aacagaacgc 5880 acattgtcag gatgactattaccaaaaaat caaaagacag caagtattgg tgaggatgta 5940 gagaaactgg aacttttgtgcactgtttat gagaatgtaa aatggagcag ctgctgtgga 6000 aaagagtatg caggttcctcaaagagtaaa accaagatgt ggaaacaact aaatgcccat 6060 cagtggatga aggggtagacaatatgtggt atatacatac catggagtac tattcagcct 6120 ctaaaaaaaa aaaaggaaattctataacat gcaacagcat ggatgaatct tgaggacatt 6180 ttgctaatga aataaggcagtcatagaaag acaaatactg cacgactcca cttatatgag 6240 ataccaaaaa tagacaaattcatagaatca aagagtacaa tggaggttac ctggagctgc 6300 agggcgggaa acgaggagttactaatcaac gaacataacg ttgcagttaa gtaagatgaa 6360 taagctctca agatcagctgtacaacactg tacctagagt caacaataat gtattgtaca 6420 cttaaaaatt tgttaagggtagattaacaa atgtagtaga tccacaaatg tggttaagtg 6480 ttcttaccac agtaaaataaaaaaagaata tcaagcccag gagttcgaga ctagcctggg 6540 taacatggtg aaaccctgtctctacagaaa atacaaaaat tagccagctg tggaggtgca 6600 ctcctaggga ggctgaggtgggaggcttgc ttgagcccag gaggtcaagg ctgcagtgag 6660 ccatgattgc accactgtactccagcccag atgacagagc aagacaccac cccccccaaa 6720 aaaagaaaaa gaatatcaaacattttaaaa gatcagatac gcaagaacaa caacaaaaaa 6780 gagatgaaca gagcatcgaccctcatctag tgggattctt ggtctaactg aaaaacagac 6840 attgagagac aaacaatgacagtgatgtga tcacagcaat tacacaggta tcccctgggg 6900 actgcagaag aaaggaggaatgcctaactt tcagaaaata gagaaagcgt caaacagttg 6960 gtgaaagcct tccaaaactagagagaactg cacacaccaa atcacagaaa gaagaaaagc 7020 cgtgggagat tctgggacccaccggctatt tttgatggct gaacaccctg ctgcaggaga 7080 gacaggagct ggaaagcatggtgggatgaa acctcaaaca gctttgcctg cattgcttaa 7140 gatgactggg cttgattaactctagtcaat ggggacaatt caatcaaaga agaaagatgc 7200 tcaaattcac attttagaatgattttttat ggcagtatgg ggaatagatt aaaagagagt 7260 gaagctggag gcaagaaacttgttaagagg caactgaaac agtctagatg ataaataata 7320 aactgacaga gtgactagaaaaatcagaac aggctgaatc aacagatacc tagatgaaaa 7380 taacaggact tgatcaccagttgtatcttg gagaggaagg agttgtttcc ttgctttccc 7440 tacgactggg aatacggaaggtttgccgtg tgtattggtt atatactggt gtgtagccaa 7500 tcactgacaa ccatttagcagcttaaaaca caaaggctta tctcccagtt tctgtgggcc 7560 aggaatctaa gataggcttagctggctggt tctggctcag agtttctcaa gaggttgcaa 7620 tcaagatgtc agctggggttgcatcatctg aaggctcaac tggggccgga gggtccactt 7680 ccaaggagtt cactcacctgcctgacaagg cagtgctggt tgttggcagg agatctcaat 7740 tcattgccaa gtgagcctctctatagcatt gctggaacat cctccccatc tggcagttgg 7800 cttctctcag catgagtgatctgagagaga gagcaaggag gaagccacag tgttcttcct 7860 actcctactc ctaacactatggacctactc ctaacactct cacttctgcc ttattccatt 7920 agttagaaag ggaactaagctccacctctt gaaataagaa gtgtcaaaga atttgtggat 7980 atatttaaaa atcatcacactgtggaagtg gatagggggt tcaattaatg ctgaacttga 8040 aatgcctgag acattcaaatgtccaacagg caatgaacat acccatagat ggtcatgact 8100 ttagcaagaa tagaggaagatcacagaatt aaggaggaat tgaaaggtaa aagaagtgga 8160 gtcagattcc ccctgaaaagtgagccatga aaggaacttt aactattgag ttagaggtca 8220 gagtaggaaa tttcggtggaattctttttt aaagaaagga accatataag catgttttga 8280 ggtagaggga gaataaatcagtagacaggg agaggtaaaa aacataaatg ataggggata 8340 gttgacaaag gtcttggcagaatcccttac ccattgactt ggggccaaga gagggacact 8400 tctttgtttg agggataaggaaaataagaa agaatgggtg ctatttagtg tggtcctgtc 8460 tctagggcaa acgcataggtaacaaactgt gtgtgttagg aatatagatg tgacctcaca 8520 ttgagattct cacctcaaatccattttgtt gttacctgta ccttcctacc ttctcttttt 8580 gctacatgca gactgctgttttgtcttcct ggcctgttcc aggtttcagc attctggcat 8640 atctgctacc ctgttcccaaacctctctag agtccatgct ccttccttgg atagtgtttg 8700 attgggccac gtatctaagaagtgatgcct tcagttaggc ctgagaacct cctctatgga 8760 aatctccatc agtgaccctgacagacttgg tatcttggag atgtcactgc tcccagcctg 8820 tggtctagga gaatctcagcctgggcctct agtagtatgg ataaggcgtt aaggtatctt 8880 tgaaccagag tctgtcatattcctcaatgt gggacagata aaacagtggt agtgctggtg 8940 tttctgagct agaactctggtttttggtct agattctttg atgtatgacc tttcagaggt 9000 attaaaattt gttctaatacaatgttcaat acaaatgtag ttccttttct gttaggacct 9060 caacaaaaca tgaccaactgtagatgaaca ttaaactatg acaattcatg gaaatgaata 9120 cagtaatacc tgcggttcccccattttagc agtcactatg gtgacatttg gcacaaatgg 9180 ctatttaagg gtgcttttgttaaaacctac catcttacta ggcacatgat attgaaacta 9240 atgaaataat ggagaaacttcttaaaaact tttaatgaat aaagtgatga agtgataata 9300 ttttagctgc tatttataaagtgactatta caggtcaaac attcttctag ggtttttttg 9360 ttgaagttgt cacatttaatccttaataac ccactatgag tcaggtattc ttctctcccc 9420 tttggacagt tggggaaatgggggtcagag aggttaggta atttgctcag ggccacacaa 9480 cctgcatgta gaaaatctgagatttgtaca ggaacgtatc aaactctgaa gtccatgctt 9540 ctattttccc atgctgcctttctaataaaa ggtaactaat gctactggat gctgccccca 9600 aagtgagtca ctttcaccccaccctacttg attttctcca taaaactaat cacatcctga 9660 caacttattt attgctgatctcccccacta gattataaac tcaataaaag caagatcctt 9720 gtctgctgaa tatcagtacctaaaacgctg tctagcacag agcaagtaat taatatttgt 9780 tgaatgaaca aataaaggaaaaaaattcaa aggaagaaaa agccctaaaa cagatgttta 9840 cctaaacata cattttaaaagaaagcatat aacaaattca ggacagaatt taaatttgat 9900 tttttaaaga aataaccaagtgctagctgg gcacagtggc tcacacctgt aatcctagca 9960 ctctgggagg ccgaggcaggcagatcactt gaggtcaaga gttcaagacc agcctggcca 10020 acatggtgaa acctgtctctactaaaaata cagaaattat ccaggcatgg tggcaggtcc 10080 ctgtaacccc agctactcaggaggctgagt caggagaatt gcttgaaccc aggaggcaga 10140 ggttgcagtg ggccaagattgcaccactgc actccagcct gagtaacaaa gcaagactct 10200 gtctgaagga gaaggaaagaaagaaggaaa gaaggaaaga aggaaagaag gaaagaagga 10260 aagaaagaaa gaaagaaagaaagaaagaaa gaaagaaaga aagaaagaaa gaaagaaaga 10320 aagaaagaaa aagaaagaaagaaagaaaga accaagtgct tatttgggac ctactatgct 10380 atgtttttcc atgcacgctattttcagtaa agcagttagc aaacttgcaa gatcataaca 10440 acaaatatat gcttctataactctaaaatt gtgctttaag aagttcctct ttaccagctc 10500 atgtatgcat tagttttctaagagttacta gtaacttttt ccctggagaa tatccacagc 10560 cagtttattt aaccaaaggaggatgcttac taacatgaag ttatcaaatg tgagcctaag 10620 ttgggccagt tcatgttaatatactccaga acaaaaacca tcctactgtc ctctgacaat 10680 tttacctgaa aattcattttccacattacc aaggagccag ggtaggagaa tatagaaaga 10740 ccacccaaga atccttacttctttcagcaa aatcaattca aagtaggtaa ctaaacacat 10800 gccctaacaa tgaatagcagattgtgctca gaagaatgat ctacaacatc ttactgtgaa 10860 ggaactactg aaatattccaataagacttc tctccaaaat gattttattg aatttgcatt 10920 ttaaaaaata ttttaagcctaaattttaaa aggtttgata ttggtacatg aatagacaaa 10980 cagacatgga ctagaccaagaattaggttc aaacatatac aggaatttaa tatacgataa 11040 atctagtatt ccaaaggaaccaacaaatgg tgttcagaca gcaggatagg catcaggaaa 11100 aacacagttg ggcaccctaccttactccta acaccaggag taactgaagg agcaccaaat 11160 atttatttat tttaattatagttttaagtt ctagggtacg tgtgcacaac atgcaggttt 11220 attacatagg tatacatgtgccatgttggt gaggagcacc aaatatttaa aagaaaaaaa 11280 ttggccaggg gcggtggctcacacctgtaa tcccagcact ttgggaggcc aaggtgggca 11340 gatcacctga ggtcgggagttcgagaccag cctgagcaac atggagaaac cccatctcta 11400 ctaaaaatac aaaattagccaggcatggtg gcacatgcct gtaatcccag ctacttggga 11460 ggctgaggca ggagaatagctttaatctgg gaggcacagg ttgcggtgag ctgagatatt 11520 gcactccagc ctgggcaacaagagcaaaac ttcaactcaa aaaaattaat aaataaataa 11580 aaataaagaa agaaaagaaaaaaatgaaaa tagtataatt agcagaagaa aacaccgtag 11640 aatcctcgga ctcttaggatggggaatgcc tataatataa aaaccctgaa gttataaaag 11700 agaaaatcac ctacatacaaaccaaatctt tctacatgcc taaaacatag cacaaacaca 11760 gctaaataat catagctgaatgaactggga aaacaaaact tgactcatat ccagacagag 11820 ttaattttcc tacacataaagagtacctat ataaacccaa caaaaaaacc accactaacc 11880 caaaataaaa atgtgacaggtaatgaacag gtagttcaca gagaatacaa atggctcttc 11940 ggcacataag atgctcagactgacttttac ttatttattt tttgagagac agggtctcac 12000 gatgttgccc aggttaggctcaaactcctg ggctcaaatg atagtaccag gactacaggt 12060 gtgccccacc gcacctggctcctcaaccac ctgtattaac aggaaatgca aaataaaact 12120 ttcaaatcta ttttacctattagaatggca aaaatttgaa aaacttcaaa catcatcatg 12180 ttggtgagaa tgtgaggagactggcactct cattttttgc tgatagcata tatatactga 12240 tggcttctat ggaaagcaatctggcagcgt ctatcaaatg tacaagtgca tatatccttt 12300 gacaaagcaa ttccactctaggaatgtgtt ctatatggtt gtgcttcctg gggctgggaa 12360 ctgggagcta agggacaggggcagaagata atcttctttt ccctccttcc ccgttaaaca 12420 tgttgaattt tatatactgtaatatattat ttttcacaaa agataatttt taagcgatat 12480 gtctgggaat ttttttttttcttttctgag acagggtctc actctgtcat ccaggctgga 12540 atgccatggt atgatctcagctgactgcag cctcgacctc ctgggttcaa gcaatcctcc 12600 cacctcagcc tcctgagtagctgggactac aggcacgtgc catcatgcta atttttgtat 12660 atacagggtc tcactatgttgcccaggcta atgtcaaact cctaggctca agcaatccac 12720 ccacctcagg ctccaaagtgctgggattac aggcgtgagc caccgcgcct ggccctggga 12780 attcttacaa aagaaaaaatatctactctc cccttctatt aaagtcaaaa cagagaagga 12840 aattcaacct ataatgaaagtagagaaggg cctcaaccct gagcaacaaa cacaaaggct 12900 atttctgaga caggaatttgctgaacaaaa tcgagggaag atgacaagaa tcaagactca 12960 cttctcggct gggcgcagtggctcacacct gtaatcccag cactttggga ggccgaggcg 13020 gacagatcac gaggtcaggagattgagacc atactggcta acacagtgaa acccagtctc 13080 tactaaaaat acaaaaaattagccgggcgt ggtggcaggt gcctgtagtc ccagctactt 13140 gggaagctga ggcaggagaatggcgtgaac ccaggaagcg gagcttgcag tgagccgaga 13200 tcacgccact gcactccagcctgggtgaca gagcaagact ctgtctcaaa aaaaaaaaaa 13260 aagactcatt tctctagatcttgagccgta ttcaaattta tctcagctta gtgagaggtt 13320 aaagcaagga atatccttccctgtgggccc tgctccttac tgaaggaagg taacggatga 13380 gtcaaggaca ccaatggagaaaagcactaa caccattatc tgatgaacat tacgtgaaga 13440 agggtaagaa gtgaagtggaattgctgaag aagtcagtga aagcggacat tcatttgggg 13500 aaatggaata taggaaatccataaaagtga ttaaaaagat gttagaggct gaggcggggg 13560 gaccacaggg tcaggagatcgagaccatcc tggctaacac ggtgaaaccc catctctact 13620 aaaaatacaa aaaattagccaggcgtggtg gcaggcacct gtagtcccaa ctactcggga 13680 gactgaggca ggagaatggcatgaacctgg gagacggagc ttgcagtgag ccgagatcac 13740 gccactgcac tccagcctgggtgacagagt gagactccat ctcaaaaaaa aaagttagat 13800 acgagagata aagatccaacagacacacaa ctgctaattc tgaacagaac aaaacaaatg 13860 gcacaggaaa agaaaatttaagatataaca ccggaaaact ttcctgaaat tgagtaactg 13920 aatctatagc ttgaaagggtttagcatatg ccaagaaaaa tcagtagagt ccaaccagca 13980 caagacacat ctagcaaggctggtgattct accaacacag agaaagaagt gggtgaccca 14040 taatgcggaa aaaggcagaccatctgcagt cttctccaga acactggagt ctgaagacaa 14100 aagaatgctg cctactgagccagaagggag agaaagtgac ccaacacatc tttaccaagt 14160 tagaatgtca cgcattatttaaaggctgca aaagccatga aagacatgaa agaacacaag 14220 catttacaac atgaaagaacacaagcattc tcatactcaa gaatccttaa gaaaaatgta 14280 gtcctaatcc agcccactgaaagttaaatg tacttaatgt gctcattaat gggaacttca 14340 tagcttcaaa tcagtctggtcccatctacc aacatctctc gcccggcttt cctgcaatag 14400 tcagcacctt tccctcctcccagtcttgtc ccctggagtc tgctctcagc atagcagagt 14460 gaccacatca acacccaagtcagagccctc cagtgcgcac tggtctacaa agcccttccc 14520 accccccacc ccacgtgccctccggatcct tgtgacgtgt ctcctgcata ccctagcagc 14580 cctggcctcc tcactgcccctcctgtacat caggaaggcg actccttgag tcttggctct 14640 ggccgcctcc tccacctgcagtgagttaac tcccttacct actctaggtc attgctcaaa 14700 tgtcagcatc tcaatggggccctccctgac taccctattt aaattctaca tactcccctt 14760 gaccccatgg acctcactcaccctattcca cttttattct tacaatttag cacttgttct 14820 cttctaacgt attctaagacttactcattt attacattgt ttgccacccc ctctagtaca 14880 taaactccag aggggcagggatttctgtct atttattcat ttctttatcc ctaggacata 14940 gaacagggca tagttcagagtattcaatgt tatcaatgaa tgaactagca gtagtaccag 15000 ttccagttag gcacagaattaaatctaaat agaattaaat ctcatggtct gggttaacta 15060 tggatagaaa attagatataattttaagaa gcctagaaag aaaaaattaa taatgtaaaa 15120 ataatattaa tttgataataataacaaaaa ctctgccagg cactgtggct caaatctgca 15180 atcccagcta ctcaggaggctgaggtggaa ggatcacttg agaccagagt tcaagactca 15240 gcctaggcaa cacggcaagaaactgtctct aaaaaaatta aaacttaaat ttttaaaaaa 15300 gaattctcaa agcgtcacaaaaactggaga ttaaggtaca ggaagtgtga agtaatatta 15360 ctatgctaat ggttttttttttttttagaa aggtataacc aaaagatttc tttctcaagt 15420 cgataaactg agaaagataagcatatcttc caattaacag agggggagga aaagccagat 15480 acaacaaaat aagatataaattagtttcca gttgaaaaca agagtaggag ttattttgca 15540 tcacctcacc tgtgacctcccccagcccaa aaaacactac tgataaacag ggtagaaaag 15600 catcatctca gataaagcaggaaaaactgc cacagtctca aaccacaaac tataagcaca 15660 cacctggcca accctgccaagtctgggctc agtaggagga acgtgctgag agctaggatg 15720 taccaactta gacattctgtgggatacaga tgtccctgga agggtcacac catctcaaag 15780 gcacctgtaa tgcccactgattacagccac catatgtgag agagaaactc agggcactta 15840 gagagtataa caagaaccttatgtcatctg agatgaggaa tcctcagccc tgcaaattaa 15900 ccaactcttt agaacaactggcaaaacata aatatccaca acttttgttt cagtaattcc 15960 actcttagat atcaatccaaagtacatgag acagcagata cacacacaaa atggtattta 16020 ctgcagcatt gtttataatagcaaaaaaca agaaataatc catatgtctc aataggatac 16080 tgggtacatg agggtatgtacccatcattc aaccatcaaa aagagtgata tggatgtcca 16140 cagatggaca taaaaagctgtgtgttacgt gaaaacaaac tcaagcagca gcaggatggg 16200 cttatgatag tcagtatgagctaatttctg gaaaaaaaaa tctagtgtgt gcacagaaaa 16260 catctgaaag aacagaaacaaaactatcag cagaatattg agatgtttta ctaagttgta 16320 tatctatact gcttgtaatttttaccccaa gcaagaatta ctttttggaa aaagaaaatt 16380 caggaaataa agcatttctttaaacttcat gtttaaacaa atggtgatgg aataaaagag 16440 ttcttattca tcataaacacacacagcaca catgcacgca tgtgcgtgag cacacccttt 16500 acttgataaa taccatgttgaatattttag tctttccttt taggttctat cccttcactc 16560 aaaatgcggt tataaataaatgtacttttc atgtgccttc tgcctaaacc cactttaata 16620 taactttaca gtcccattatcattatagtc tcaaagctag actcagcctg aaactaccct 16680 ttcatttgga acccttattaaaatgccaca tacagctcct tcaaataaaa acaaacccta 16740 ggacctgaca ctaggcttcctttgttgcta ctcataatgg ccaagttctg tgcttataat 16800 acatcttctt tcattttattgctacatatc caagggtttt atatgttttt cttattatat 16860 cttaattcaa aacaccatcacgctcttttc cagatgaaaa taaggaaaag aaattgagca 16920 actgactgac ttaaaggtcataaaactata tagtagcaga gtcagcaaaa gaagaaacac 16980 acatctccca agtagaggctgaaaaccagt accattcacc tccagggtga gctatataca 17040 gattacaaag tcaccttctctaaatgttca aactgaatcc catacccata ctttaccact 17100 acctcgtaag aacagcctcagatcttgtta tagccttttt tttagcatgc tgaagccaat 17160 aaaatgcttc ccattcagcaagagaaacaa gttctgaaac actgaataat ctgcccaggg 17220 cctatgaaca tttccactgtgagaaatgtt ctccactgtg tggagaagat ccttactctt 17280 ctccacacag gcagaacattagaaaaattc ttggattcta tgatgcacag cttaggagtc 17340 tgtttagcac aatttaagtccaaatagtta ttaaatcctc ctctgttcca gaaacagtgc 17400 taaatactgt gaatataaaaattgaaaaga tactctcctg gctcccaaga aagtcagcca 17460 gatagaggag acacaggcacacaaatcact gtcacatgaa gctctacctc cctaacttca 17520 aacgagggcc taagtcaccaagaatacagt agcagttgtg actacgagta actactataa 17580 ttcaatactt tatcttcccttagaaaactc ttctcccttg gaaatttatt tgcatttcta 17640 aataccattc cttactaaaaggaagcaggg ctccttgggg aaatagctga ttctaggtgt 17700 ggactatgaa atgaaaatggtgagtctggg acatcccatg ttgcccagaa atcaaggaac 17760 tgcccaaaga ttaacagagtcatgttaaat ggacctaaga gtgaaccaga aggagctcac 17820 tttgccccgc gtggaacaatttcaagaaaa acatgacagt aatgaattat aaaacatgaa 17880 ttaaaataca tattggtactaaaaagagaa caaaaggatg tggctttgga taaagctctt 17940 cttcatggaa gaataccagctaataaatgt aaaggaaatg agagaattag aaaaattatc 18000 attttgtaaa ccttaatatattcacctaga catgctaaaa ccactgagta aaaggctgct 18060 tgggaagagg atgctcacatgatctcagag tttcacacca cagataattt attagataca 18120 ggaaggaaga tgtgatcaagcttcctgtga cccccagcca ggccccacaa cactatgtgc 18180 ctccttgtga tgtgggagctacacagcatc gcccacacag cttctcgcca aaactgtttg 18240 aagctaatca caagggaagaactggacagc ttctgaccat gagacgctcc accagacaac 18300 ttgcttggcc tctccaaagaaacttgcttg gcctctccaa agaaaactca gtttcattta 18360 aaaacaaaac taattatttaaaaacaaacg aaaagcaagt tgtggacttg agctccaggg 18420 acagagcaga catacttttccctgttcttc ccagtaagtg gtaataaaaa ccctcaacac 18480 tagatataaa acaaatataagaaggttctg gaaggggaag aggaggcaga ctatccaggt 18540 gccttgaggc ccacagaacaacccagtgat gggttcactg ggtcttcttt ttgcttcatt 18600 atctcagact tggagctgaagcagcaggca acttcaaaac accaaggggc acagattgaa 18660 aagccccaag aaaagcctgccctctctagc caaaggacca ggaaggagac agtctaatga 18720 gatggaacac atttagacagtaactgccca tttaccagca ataactgagc agggagccta 18780 gacttccagt cttgtgaggacgtaccaagg tacccaacac ccccaccaag gctgagtaag 18840 gactgcgact tttatccctgcatggcagta gtaaggagcc catccctcac ccgccagcag 18900 tgtcagggga acctggacttccactcccac ccaggagtga tgaggccctc cctgctgggg 18960 tcatgtcaga ggaggcctagtggagattca gtgacttaac cttttcccag agataatgag 19020 gccacctttc ctccctcttcccccatggtg acagtgaaag cactgtggca agcagtaggc 19080 actcctaccc ctcctagccagggaggtatc agggaggcca agtagggaac cagaataccc 19140 acaaccaccc agcagcaacaggggtccccc accccattgg gtgtcaatgg aagcagagcg 19200 gaaagcctgg atatttacccccatctagaa gtaacaagct gatgtccccc ttcttctact 19260 acaatggtgt tcaaaacaggtttaaataag gtctagagtc tgataacgta atacccaaat 19320 cgttgaagtt ttcattgaggatcatttata ccaagagtca ggaagatccc aaactgaaag 19380 agagaaaaga caattgacagacactagcac taagagagca cagatattag aactacctga 19440 aaggatgtta aagcacatatcataagcctc aacaggctgg gcgcggtggc tcacgcctgt 19500 aaccccagca ctttgggaggccgaggcagg tggatcacaa gatcaggaga tcgagaccat 19560 cctggctaac acggtgaaaccccgtctcta ctaaaaatac aaaaaaaaat agcaaggcat 19620 ggtggtgggc acctgtagtcccagctactc gggagcctga ggcaggagaa tggcatgaac 19680 ctgggaagag gagcagtgagccgagatcgc accaccgcac tccagcctgg gcaacagagc 19740 aagacttcgt cccaaaaaaaaaaaaaaaaa aaaaaaaagc ctcaacaaac aactacaaac 19800 gtgcttgaaa caaatgaaaaaaaaatcttg gcaaagaaat aaaagatata tattttggcc 19860 aggtgcagtg gctcacagcctgtaatccct gcactttggg aggctgaggc aggcggatca 19920 cctgaggtca ggagtttgagaccagcctga ccaacatgga gaaaccccgt ctctactaaa 19980 aatacaaaat tagccagtcatggtggcaca tgcctgtaat cctagctact caggaggccg 20040 aggcaggaga atcgcttgaactcaggaggt ggaggttgcg gtgagccgag atcccgccat 20100 tgcacattgc actccagcctgggcaacaag agcaaaactc catctcaaaa aaatagatac 20160 atattttaat ggaaattttagaattgaaaa atacagtaac caaattgaat ggaaagacaa 20220 catagaatgg agggggcagacaaaataatc agtgaacttc aacagaaaat aatagaaatt 20280 acccaatatg aagaacagaaagaaaataga ctggccaaaa aataaagaag aaaaaagagg 20340 agcagcagga ggaatgatggaaaaagagaa aggaaggaag gaagggaagg agggagggaa 20400 ggagtgaggg agaaagtctcaaagacctct gagactaaaa taaaagatct aacacttgtc 20460 atcagggtcc aggaaagagacaaagatggc acagctggaa acgtattcaa aaaataatag 20520 ctgaaaactt cccaaatttggcaagagaca taaacctata gattcgaaat gctgaacccc 20580 aaataaaaag cccaataaaatccacaccaa aatacatcat agtcaaactt ctgaaaagac 20640 gaaaagagaa aacgtcttgaaagcagtgag tgaaacaaca cttcatgtat aagggaaaaa 20700 caattcaagt aacagatttcttacagaaat taaggaagcc agaaggaaat gacacaatgg 20760 ttttcaagtg ctgaaagaaaagaagtgtca acacaaaatt ctagattcag taaaaatatc 20820 cttcaagaat caatgggaaatcaagacagt ctcagataaa gcaaaataag agaatatgtt 20880 gccagcagat ctcccctaaaggaatggcaa aaggaagatc atgcaacaga ccaaaaaatg 20940 atgaaagaag gaatccagaaacatcaagaa gaaagaaata acatagtaag caaaaataca 21000 tgtaattaca ataaaatttctatctcctct taagacttct aaattatatt gatggttgaa 21060 gcaaaaatta taaccctgtctgaagtgctt ctactaaatg tatgcagaga attataaatg 21120 gggaaagtat aggtttctatacctcattga agtggtaaaa tgacaacact gtgaaaagtt 21180 acatacacac acacacgtaagtatatataa atatatgtgt gtatatgtgt gtgtatatat 21240 atatatacat ataatgtaatacagcaacca ctaacaacac tatacaaaga gataataacc 21300 aaaaacaatt tagataaattgaaatggaat tctaaaaaat attcaaatac tctacaggaa 21360 gacaagacaa aaagagaaaaaaagaggagg acaaactaaa ttttttaaaa acataaataa 21420 aatggtagac ttaagccctaacttatcaat aattacataa atgtaaatga tctaattata 21480 tcaattaaaa gacagagatagcagagttaa tttaaaaaca tagctataag aaacctgctt 21540 tgggctgagt gcagtgactcacacttgtaa tcccagcact tcgggaggcc aaggcgggtg 21600 gatcacctga ggtcaggagttccagaccag cctggacaac atggtaatac cccatctcta 21660 ctaaaaatac aaaaaaattagccaggcatg gtggcacacg cctgtagtcc caactactca 21720 ggaggctgcg acacaagaactgcttgaacc cgggcagcag aggtagcagt gggccaagat 21780 tgcgccactc cagcctgaacgacagagtga gactccacct cagttgaaaa acaaaaaaga 21840 aacctgcttt aaatataccaacatatgttg gttgaaatta aaagaataaa atatatcatg 21900 aaaacattaa tcaaaagaaaggagtggcta tattaataac ataaaataga cttcagagaa 21960 aagaaaattt caagagacaggaataaaagg atcaagaaaa gatcctgaaa gaaaagcagg 22020 caaatcaatc attctgcttggagattcaac accctctctt aacaactgat agaacaacta 22080 gacaaaaaaa tcagcatggagttgagaaga acttaacacc actgaacaac aggatctaat 22140 agacatttac ggaacactctacccaacaat agcaaaataa acattctttt caagtattca 22200 ctgaacatat ccttagaccctaccctgggc cataaaacaa agctcactag tgattgccga 22260 aggcttggat ggacagtggaagagctgcat ggggagggag aaggtgacag ttaaagagtg 22320 taggatttct ttttgggataatgaaaatgt tccaaaattg attgtggtga tgttggcgca 22380 actctacaaa tataaaaaaggccattgaat tgtacgtttt aagtgggtga aacatatggt 22440 atgtggatta tatctaacgctttttaaaaa cttaacacat ttcaaagaat agaagtcata 22500 cagagtgtgc tctactggaatcaaactaga aagaggtaac tggaggataa cgagaaaagc 22560 ctccaaatac ttgaaaactggacagcacat ttctaaaatc atccgtgggt caaagatatt 22620 catttctgat attcatttttattgtttaat gtatttttaa aaatttctta agggaaataa 22680 actgactaaa aatgaatatggctgggtgcg gtggctcacg cctgtgatcc cagcactttg 22740 ggaggccgag gctggtggatcacaagatca ggagttcgag accagcctgg ccaagatggt 22800 gaaaccccgt ctcaactaaaaaactacaaa aagtagccaa gcgcagtggc gggagcctgt 22860 ggtcccagct acttgggaggctgaggtagg agaatcgctt gaacacaggc agcagaggtt 22920 gcagtgagcc aagattgtgccactgcacgc cagcctgggc gacagagact gcctcaaaaa 22980 aaaaaaaaaa aaaaagaatatcaaaatttg tgggacatag ttaaagcaat gctgagaggg 23040 aaatttataa cactaaatgtttacattaga aaagagaaaa agtttcaaat caatagtctc 23100 cactcccatc tcaagaacacagaagatgaa gagcaaaata aacccaaagc aagcaaaaga 23160 aagaaaatat aaaaataaatcagtaaaatt gaaaacagaa acacaataaa gaaaatcagt 23220 gaaacaaagt actgattcttcgaaagatta ataaaattga caaacctcta gcaaggctaa 23280 caaacaaaaa agaaagaagacacggattac cagttattag aatgaaagca taattagaaa 23340 caactctaca cattataaatttgacaatgt agatgaaatg gactaattac tgaaaaaaca 23400 caaattacca caactcacccaatatgaaat agataattgg gatagcctga taactactga 23460 gaaaattgaa tttgtaattttaacactctt aaaacagaaa cattaaactt aatattttat 23520 aaatattaga taaggtaattatacccttcc ttaacaaata aaaacgacaa attattttgc 23580 agctaaagag atgtatgtactgtgaaaaat atcttcagaa aaatagaact ttgtttgaag 23640 aataaggatt taaaaaatgtttttaactct caagaagcaa atatctgggc ccagatggtt 23700 tcactgaaga attctaccaaatgtttaatg aagaattacc accaactcta catagcatct 23760 ttgagaaaac tgaagagaagggaacatctc ccagttcatt ttatgaagtg ggtgttactc 23820 tgatactaga actgtataaggacagctact cttgacacac tgcctatggg tagctctgct 23880 ctgcaggaac agtcagaaaaaaaaaaaaaa gaagcactgg acaagggcag tataaaaaaa 23940 gaaaactggg ccaggtgcagtggctcacac ctgtaatctc agcactttgg gaggctgacg 24000 ctggtggatc acctgaggtcaggagtttga gactagcctg gccaacatgg taaaaccctg 24060 tctctactaa aatacaaaaattagccaggc agggtggtgg ggaaaataaa aaggaaaaaa 24120 aaacaaaaat aaactgcagaccaatatcct tcatgagtat agacacaaaa ctccttaaac 24180 tccttaacaa aatattagcaagtagaagca atatataaaa ataattatac accatgatca 24240 agtgggactt attccagaaacgcaagtctg gttcaacatt tgaaaacaag gtaacccact 24300 atatgaacgt actaaagaggaaaactacat aatcacatca atcaatgcag aaaaaagcat 24360 ttgccaaaat ccaatatccattcatgatac tctaataaga aaaataagaa taaaggggaa 24420 attccttgac ttgataaagcttacaaaaga ctacaaaagc ttacagctaa cctatactta 24480 atggtgaaaa actaaatgctttcccctacg atcaggaaca aagcaaggat gttcactctc 24540 attgctctta tttaacatagccctgaagtt ctaacttgtg caaaacgata agaaagggaa 24600 atgaaagacc tgcagattggcaaagaagaa ataaaactgt tcctgtttgc agatgacatg 24660 attgtctcat agaaaatgtaaagcaactag gggtaggggg gcagtggaga cacgctggtc 24720 aaaggatacc aaatttcagttaggaggagt aagttcaaga tacctattgc acaacatggt 24780 aactatactt aatatattgtattcttgaaa atactaaaag agtgggtgtt aagcgttctc 24840 accacaaaaa tgataactatgtgaagtaat gcatacgtta attagcacaa cgtatattac 24900 tccaaaacat catgttgtacatgataaata cacacaattt tatctgtcag tttaaaaaca 24960 catgattttg gccaggcacagtggctcata cctgtaatcc cagcatttta ggaggctgag 25020 gcgagcagaa aacttgaggtcgggagtttg agaccagaat ggtcaacata gtgaaatccc 25080 gtctccacta ataatacaaaaattagcagg atgtggtggc gtgcacctgt agacccagct 25140 acttgggagg ctgaggcacgagaattgctt gaacaaggga ggcagaggtt gcagtgagct 25200 gggtgccact gcattccagcctggtgacag agtgagactc catctcaaaa aaaataaaat 25260 aaagcatgac ttttcttaaatgcaaagcag ccaagcgcag tggctcatgc ctgtaatccc 25320 accactttgg gaggccgaggcaggcagatc acaaggtcag gagtttgaga ccagcctgac 25380 caacatggtg aaaccccatctctactaaaa aatatataaa ttagccaggc atgtgtagtc 25440 tcagctactc aggaggctgaggcaggagaa tcacttgaac ccggaggcag aggttgcagt 25500 gttgagccac cgcactccagcctgggtgag agaacgagac tccgtctcaa aaaaaaaaag 25560 caaaataacc taattttaaaaacactaaaa ctactaagtg aattcagtaa gtctttagga 25620 ttcaggatat atgatgaacatacaaaaatc aattgagctg gacaaaggag gattgtttta 25680 ggtcagtagt ttgaggctgtaatgcacaat gattgtgcct gtgaatagct gctgtgctcc 25740 agcctgagca gcataatgagaccacatctc tatttaaaaa aaaaaaaatt gtatctctat 25800 gtactagcaa taagcacatgggtactaaaa ttaaaaacat aataaatact gtttttaatt 25860 gcctgaaaaa aatgaaatacttacatataa atctaacaaa atgtgcagga cttgtgtgct 25920 gaaaactaca aaacgctgataaaagaaatc aaagaagact taaatagcgt gaaatatacc 25980 atgcttatag gttggaaaacttaatatagt aaagatgcca attttatcca aattattaca 26040 caggataaca ttattactaccaaaatccca gaaaaatttt acatagatat agacaagatc 26100 atacaaaaat gtatacggaaatatgcaaag gaactagagt agctaaaaca aatttgaaaa 26160 agaaaaataa agtgggaagaatcagtctat ccagtttcaa gacttacata gctacagtaa 26220 tcaagactgt gatattgacagagggacagc tatagatcaa tgcaaccaaa tagagaacta 26280 agaaagaagc acacacaaatatgcccaaat gatttctgac aaaggtgtta aaacacttca 26340 acgggggaag atatgtctctcattaaaggg tgtagagtca ttgcacatct ataggcaaaa 26400 agatgaacct gaacctcacaccctacagaa aaattaactc aaaatgactc aaggactaaa 26460 cataagatat acatctataaaacatttaga aaaaggccac gcacggtggc tcacgctcgt 26520 aatcccagca ctttgggaggccaaggcagg tggatcacct aaggtcagga gtttgagacc 26580 agccggatca acatggagaagccccatctc tactaaaaat acaaaattag ctggacgtgg 26640 tggcacatgc ctgtaatcccagctacttgg gaggctgagg catgagaatc gcttgaaccc 26700 ggggggcaga ggttgcggtgagccaagatc acaccattgc actccagcct gggcaacaag 26760 agcaaaactc caactcaaaaaaaaaaaaaa aaaggaaaaa tagaaaatct ttgggatgta 26820 aggcgaggta aagaattcttacacttgatg ccaaactaag atctataagg ccagtcgtgg 26880 tggctcatgc ctgtaattccagcactttgg tcaactagat gaaaggtata tgggaattca 26940 ctgtattatt ctttcaacttttctgtaggt ttgacatttt tttagtaaaa aattggggga 27000 aagacctgac gcagtggctcacacctgtaa tcccagcact ttgggaggcc ggggcaggtg 27060 gatcacacgg tcaggagttcgagaccagcc tggccaacat ggtgaaaccc cgtctctacc 27120 aaaaatataa aaaattagccgggtgtcatg gtgcatgcct gtaatcccag ctactgagga 27180 ggctgaggca ggagaatcacttgaacctgg gaggtggaag ttgcagtgag ccgagattgt 27240 gccactgcac tccagccttgggtgacagag cgagactccg tctcaaaaga aaaaaaaaaa 27300 aaagaatatc aaacgcttactttagaaact atttaaagga gccagaattt aattgtatta 27360 gtatttagag caatttttatgctccatggc attgttaaat agagcaacca gctaacaatt 27420 agtggagttc aacagctgttaaatttgcta actgtttagg aagagagccc tatcaatatc 27480 actgtcattt gaggctgacaataagcacac ccaaagctgt acctccttga ggagcaacat 27540 aaggggttta accctgttagggtgttaatg gtttggatat ggtttgtttg gccccaccga 27600 gtctcatgtt gaaatttgttccccagtact ggaggtgggg ccttattgga aggtgtctga 27660 gtcatggggg tggcatatccctcctgaatg gtttggtgcc attcttgcag gaatgagtga 27720 gttcttactc ttagttcccacaacaactgg ttattaaaaa cagcctggca ctttccccca 27780 tctctcgctt cctctctcaccatgtgatct cactggttcc ccttcccttt atgcaatgag 27840 tggaagcagc ctgaagccctcgccagaagc agatagtgat gccatgcttc ttgtacagcc 27900 tacaaaacca tgagcccaataaaccttttt tctttataaa ttatccagcc tcaggtattc 27960 ctttatagca agacaaatgaaccaagacag ggggaaatca acttcattaa aataatctat 28020 gcagtcacta aacaaataagaacaagaggc tccagaagtg ggaagccaat acccagagtt 28080 cctacaatac agtatctgaaaagtccagtt tccaaccaaa aaatatatat atacaggccg 28140 gacatggtag cttatgtctgtaatcccagc actttgggat gctgaggcgg gcagatcacc 28200 ctaggtcagg agttcgagaccagcctggcc aatatggcaa aaccccgtct ctactaaaaa 28260 tacaaaaatt agccaggcatggtggtggat gcctgtaatc ccagctactc gggaggctga 28320 ggcagggaat cacttgaacccaggaggcag aggttgcagt gagccgagat cacgccactg 28380 aactccagcc tgggcaacaaagtgagactc cacctcaaaa aaaaaaaaaa tatacatata 28440 tatatgtgtg tgtgtgtgtgtgcgcgcgtg tgtgtatata cacatacaca tatatacata 28500 tatacagaca cacatatatatatgaagcat gaaaagaaac aaggaagtat gaaccatact 28560 ttctgtggtt atgataggatggggtatcac gggggaagta gacaagggaa actgcaagtg 28620 agagcaaaca gttatcagatttaacagaaa aagactttgg agtaaccatt ataaatatgt 28680 ccacagaatt aaagaaaagcgtgattaaaa aaggaaagga aagtatcata acaatattac 28740 tccaaataga gaatatcaataaaggcatag aaattataaa atataataca atggaaattc 28800 cggagttgaa aggtagaataactaaaattt aaaattcact agagaaggtt caacactata 28860 tttgaactgg cagaagaaaaatttagtgag acaaatatac ttcaatagac attattcaaa 28920 tgaaaaataa aaagaaaaaagaatgaagaa aaataaacag aatctcagca aaatgtggca 28980 caccattaat cacattaacatatgcatact gagagtaccg gaagcagatg agaaagagga 29040 agaaaaaata ttcaaatgatggccagtaac ttcctagatt tttgttttaa agcaataacc 29100 tatacaatca agaaactcaatgaattccaa gtaggataaa tacaaaaaga accacaaaca 29160 gatacaccat ggtaaaaatgctgtaagtca aaaacagaga aaatattgaa agcagctaga 29220 ggaaaactta taagagaacctcacttacaa aagaacatca cttataaaag aaccacaata 29280 atagaaacag ttgacctctcatcagaaaca atgaatgata acatatttga agtgctcaaa 29340 gaaaaaaaat aaagattcctatatacgaca aagctgtctt tcaaaaatat acatccaaaa 29400 ggattgaaac cagggtcttgaagagttatt tgtacatcca tgttcatagc agcattattc 29460 acaatagcca aaaggtagaagcaacccaag ggtccatcga caaataaata aaatgtggta 29520 tatgtataca caatggaatttattcagtat taaaaaggaa tgaaattctg acacatgcta 29580 caacatggct aaaccttgagaacactatgc taagtgaaat aagccagcca caaaaggaca 29640 aataccatat tacttcacttgtatgaaata cctagggtag tcaaattcag agatagaaag 29700 taaaacagtg gttgccaagggctgagggag ggagtaacgt ggagttattg ttgaatgggt 29760 acagaatttc agttttgcaagataaaaaga gttctggaga cagatggtgg tgagggtggt 29820 acaacaatac aaatatactttatactactg aacagtatac ttaaaaatga ttaacatggt 29880 gaaaccccgt ctctactaaaaatacaaaaa aattagctgg gtgtggtggc gggcacctgt 29940 aatcccagct acttgggaggctgaggcagc agaattgctt gaaaccagaa ggcggaggtt 30000 gcagtgagct gagattgcgccaccgcactc tagcctgggc aataagagca aaactccgtc 30060 tcaaaaaata aaaaataaaaaaaatttaaa aatgattaag caggaggcca ggcacggtgg 30120 ctcacaccta taatgccagcactttgggag gccgaggcag gcgatcactt gagaccagga 30180 gtttgagacc agcctggccaacatggcaaa accctgtctc tgctaaaaat acaaaaatta 30240 gccaggcatg gtggcatatacttataatcc cagctactgg tgagactgag acacgagaat 30300 tgcttgaacc caggaggcagagattgcagt gagtcgagat cgcgccactg aattccagcc 30360 tgggcgacag agcaagattctgtctcgaaa aaacaaaaac aaaaacaaaa agcaaaacca 30420 aaaaataatt aagcaggaaacgagattgct gctgaggagg agaaagatgt gcaggaccaa 30480 ggctcatgag agcacaaaacttttcaaaaa atgtttaatg attaaaatgg taaattttat 30540 atgtatctta ccacaaaaaaaagggctggg gggcaggaaa tgaaggtgaa ataaagacat 30600 cccagagaaa caaaagtagagaatttgttg ccttagaaga aacaccacag gaagttcttc 30660 aggctgaaaa caagtgaccccagagggtaa tctgaattct cacagaaaat tgaagcatag 30720 cagtaaaggt tattctgtaactatgacact aacaatgcat attttttcct ttcttctctg 30780 aaatgattta aaaagcaattgcataaaata ttatatataa agcctattgt tgaacctata 30840 acatatatag aaatatacttgtaatatatt tgcaaataac tgcacaaaag agagttggaa 30900 caaagctgtt actaggctaaagaaattact acagatagta aagtaatata acagggaact 30960 taaaaataaa attttaaaaaatttaaaaat aataattaca acaataatat ggttgggttt 31020 gtaatattaa tagacataatacaaaaatac cacaaaaagg gaagaagaca atagaactac 31080 ataggaataa cattttggtatctaactaga attaaattat aaatatgaag tatattctgg 31140 taagttaaga cacacatgttaaaccctaga tactaaaaag taactcacat aaatacagta 31200 aaaaaataaa taaaataattaaaatgtttg tattagtttc ctcagggtac agtaacaaac 31260 taccacaaat tgagtggcttaacacaactt aaatgtattt tctcccagtt ctggaggcta 31320 aacacctgca atcaaggtgagtacagggcc atgctccctg tgaaggctct aggaaagaat 31380 cctcccttgt ctcttccagcttccagtggt tctcagtaac cctaagtgct ccttggcttg 31440 tagctatatc attcctagcaaccagaaaga agaaaataat aaagattatg gcaaaaaata 31500 atgaaatcaa aaggagaaaaatggaaaaaa ataaataaaa ccaaaagcta gttctttgaa 31560 aagatcaacc aagttaacaaaccttttaac tagactgaca aaaaggaggt aagactcaaa 31620 ttactagaat cagaaataaaagaggggaca ttactaatga gggattagaa aagaatacta 31680 cgaacaaatg tgtgccaacaaattagaaaa cttagatgaa atggacaggt tcctaggaca 31740 acatcaacta ccaaaatttactcaagaaga aagagacaat ttgaatgagc tataacaagg 31800 gaagagactg aattgacaaccaagaaacta tccacaaaga aaatcccagg cccagaagat 31860 ttcactgtga aattctttcaaacttataaa tataaattaa catcagttct tcacaaactc 31920 ctccaaaaaa aagaacagatctctatttac aggcgatacg atctttagaa aatcctaagg 31980 gaactactaa gacactatgataactgataa acaagttcag caaggctgca ggatagaaaa 32040 ccaatataca aaaatctattatatttctat acacttgcag tgaacaaccc aaaaatgaga 32100 ttaagaaaat aattcaatttacaataacat caaaaagaat aaaaacactc aaaaataaat 32160 ttattcaagt aagtgcaaaacttatactct agaagctaca aaacactgtt aaaagaaatt 32220 aaaggtttac ataaatgaaaaactatccca tgttcatgga tcaaaagact tattactggc 32280 aatgctctcc aaattgatctataaattcaa caaaatcctt atcaaaatcc cagatgaggc 32340 tgggggtggc ggttcatgcctgtaatccca gcactttggg aggctgaggc acgcagatta 32400 cctgaggtcg ggagctcgagatcagcctga ccaacatgga gaaaccctat ctcttctaaa 32460 aatacaaaat tagtcaggcgtggtggcaca tgcctataat cccagctact cgggaagctg 32520 aggcaggaga atcgcttgaacccaggaggc agaggttgca gtgagccaag atcgtgccat 32580 tgcactccag cctgggcaacaagagcaaaa ttccatctca aaaaaaaaaa aaaaaaaatc 32640 ccagatgact tcactgttgaaattgaaaag attattctaa aattcacatg gaattgcaag 32700 accttgagaa tagccaaaacaaacttgaaa aacacgaaca aaatatagga tgactcactt 32760 gccaattgca aatgttacgacacagcaaca gtaatcaaga ctgtgtggta ctggcaaaag 32820 acacatacat acatacatatcaatggaata taattgagag tacagaaaca agcctaaaca 32880 tctatggtaa gtgcttttctatttttttct tttttttttt cttttttgta gagatagaat 32940 ctcaccatgt tgcccaggctggtcttcaac ttctgggctc aagcaatcct cccactgtgg 33000 cctcccaaag tgctgggataactggcatga gccaccacat ccagcccaga tgattttcaa 33060 aaaagtcaac aagaccattcttttcaacaa ataggtctgg gatgatcaga tagtcacatg 33120 aaaaaaaaaa tgaagttggaccctccatca cactaaagtg ctgcgattat aggcatcagc 33180 caccacatcc agcccaaatgattttcaaaa aggtcaacaa gaccattctt ttcaacaaat 33240 aggtctggga taatcagatagtcacatgaa aaaaaaaatg aagttggacc ctccatcaca 33300 ccatatgcaa aaattaattcaaaaatgaat tgatgactta aacgtaagag ttacgactgt 33360 aaaactctta gaaggaaacatacgggtaaa tcttaaagac gttaggtttg acaaagaatt 33420 cttagacatg acaccaaaagcatgaccaac taaggtaaaa tagggtaaat tgtacctacc 33480 aaaatgaaaa acctttgtgctggaaaggac accatcaaga aatggaaagc caaaatagcc 33540 aaggcaatat taagcaaaaagaacaaagct ggaggcatca tactacctga cttcaaagca 33600 acagtaacca aaacagcatggtactagtag aaaaacagac acatagacca atggaacaga 33660 ataaagaacc caaaaataaatccacatatt tatagtcaac tgatttttga caatgacacc 33720 ccttcaataa atgatactaggaaaactgga tatcgatatg cagaagaata aaactagacc 33780 cctatctctc accatatagaaaaatcaact cagactgaat taaagacttg aatgtaagac 33840 ccaaaactat aaaactactggtagaaaaca taaggaaaaa cgcttcagga cattggtcca 33900 ggcaaagatc ttatggctaaaacctcaaaa acacaggcaa caaaaacaaa aatggaaaaa 33960 tagcacttta ttaaactaaaaagctcctgc acagcaaagg aaacaacaga atgaaaagac 34020 aacctgtaga atgggagaaaatatttgcaa actatccatc catcaaggga ctagtatcca 34080 gaacacacaa gtgactaaaacaactcaaca gcaaaaaagc aaataatctg gtttttatat 34140 gggcaaaaga tctgaataaacattctcaaa ggaagacata caaatgtcac tatcattctg 34200 ccagtaccac actgtcttgattacttgtta gtgtataaat ttttaaattg ggaagtgtga 34260 gtcatcctac actttgttcttgtttttcaa gtttgttttg gctattctgg gagccttgca 34320 agtataaaat agccaacaagtatgaaaaaa tgctcaccat cactaatcat cagagaaata 34380 aaaatcaaga ccactatgagatatcctctc actccagtta gaatggctac tatcaaaaag 34440 acaaaatata atggatgctggcaaagattt ggagaaaggg gaactcctat acactgtggg 34500 tagggatgca aattggtaatggccattatg gaaaataata ctgaggtttt tcaaaaaact 34560 gaaaatagaa ctaccatatgatccagcaac cctactactg ggtatttatc caaaggaaag 34620 aagtcagtat actgaagaaatatatgcact ctcatgttaa ttgcaacact gttcacaaca 34680 gccaagacag ggaataaatctaaatgtgca tcaacagatg aatggataaa gaaaatgtgg 34740 catatacact caatagaatactattcagcc attaaagaag aatgaaatcc tgtcatccca 34800 gcaacatgga tgaacctggaggacattata tttaatgaaa taagtaaagc acaaaaagat 34860 aaacagtaca tgttctcactcagacatggg tgctaaaaag aaaatggggt cacagaatta 34920 gaaggggagg cttgggaaaagttaatggat aaaaatttac agctatgtaa gaagaataag 34980 ttttagtgtt ctatagaactgtagggcgag tatagttacc aataacttat tgtacatgtt 35040 caaaaagcta gaagagattttggatgttcc cagcacaaag gaatgataaa tgtttgtgat 35100 gatggatatc ctaattaccctgattcaatc attacacatt gcatacatgt atcaaattat 35160 cactctgtac ctcataaatatgtataatta ttacgtcaac aaaaaaagga aaaaaaagaa 35220 aattaagaca acccacataatggaagaaat aaaatatctg caaattatat atatctgata 35280 aatatttaat atttataatatataaagaac tcctacaact caagaacaac aacaaaacaa 35340 cccaattcaa aaatgggtaaaagccttgaa tatacactta tctaaagact atatacaatt 35400 ggccaataaa gacacgaaaagatgctcaac atcactagtc atcagggaaa tataaatcaa 35460 aaccacaatg tagaatgtagacaccacttc atatgcacta ggatggctag aataaaaagg 35520 taataacaaa tgttggtaaggatgtgaaaa aatcagaaac ctcattcgct gctgttggga 35580 atgtaaagtg atgcagccactttggaaaac agtctggcag ctcctcaaat tattaaatac 35640 agagttaccg tatgacccaggaatattcct cctgggtcta taaccaaaaa aatgaaaaca 35700 tatatccaca taaaaacttgtacatgggca tttatagcaa cattattcat aacagcaaag 35760 gtggtaagaa cccatatgcccatcatctga tgaacaggta aataacatgc ggtattatcc 35820 atacactaga atattatctgcccatacaag gagtgacatc cagctacatg ctacaaggat 35880 gaatctcgga aaccttatgctaagtgaaag aagccagtca caaatgacca cagattatga 35940 ttccatgcat cggaaatgaccagaataggg aaatctatag agacagaaag tagattagtg 36000 gttgggtggg gctgggaggacaggtagtac actactttcc cagaactact ggaacaaagt 36060 accacaaact ggggagcttaaacatagaaa ttgatttcct cacagttctg gagactagga 36120 ctctgagatc aaggtgtcagcagagctggt tctttctgag ggccctgagg caaggctctg 36180 tcccaggcct ctctccttggctggcaggtg gccatcttct ccctgcgtct tcacatcatc 36240 ttttctctgt gtgtgcccatgtccaaattt tgattggctc attctgggtc atggccaatt 36300 gctatgcaca aagtgaagtctacttccaaa agaagggaag agggaacact gactaggcta 36360 aacttatagt cattttaatgtccgcttttc ctatgagatt gtgaacacac agaagtaggg 36420 tttttatcta cattgtgcaaagtttaataa gaaaaataga attcaagaga agcagttcaa 36480 tagcaggaat ttaatatgggaactaattac aaggtttagg gcaggactaa aaagccagtt 36540 gggatggtga gccaacccagagattagcaa cagtgggacc ccatctacct accacccatg 36600 aagctggaag gataaaggaggggctattat cagagtccac aagccagtgt cagagtcctt 36660 ggctggagct gggaccaccctagagacact gtgcaaagca gaaaacaagg gggaaaaacc 36720 ctgacttctc ccttcctcccacctttcaat ctcccactag tgcttcctac tagccatact 36780 tggccagaga cagtgacaaggaacactgca aaatgaagtt tgtaggaatc atctccctct 36840 gagacagaga aatatggaagggtagaaaat gaatcagagg ataaagagaa aaaaccctga 36900 gtactatctt atttatctttgtatctccag tgcctaatct gtctctcaaa aaaggaaagc 36960 aattgagaga aactgaaaactccaattgaa atgaaagaat ggagaattac tggactagaa 37020 gagaagagaa aaatttattccgcatagagt aaacaagaat ggattcacaa aggacgtgat 37080 gaatgaaaag ctataatcagcaaagatttg ccagagaaat taaaaagtgg taaactcagc 37140 cacgctgtac aacctgaaggcacaatgcat gaaaacgttt caagaaatga caagatttga 37200 agtcaaattc taagtgcttttccagaatct ctcaagacga ttatatagct accccatttt 37260 attaaataaa atggaaacttactaaacttt ccccttgtat taaactaaca tatgtcctaa 37320 tagcaaacga ttctggaattcctagagtaa aatatatttc gtcaaagtgt attgctcttt 37380 taatattctg ctgacctccttttgctattt aggatatttg tatacacatc acacgtaaat 37440 ttggtctata gtttacatctacgggcttat actgttcttt ttttcatttt tttaaaattt 37500 ccaaccccca gtatccatatactgctctct atcagggtta ttttaacttt gtaaaatcag 37560 ctgagatgct ttccatgtttttttttttta ttttctgcca catttgaata gcataggagt 37620 taccaccatc aaccttggattatttaagca ttcacgattc cacgtgtgga ttttttattc 37680 agagtctttc ttgtcattcctgctatcagc acagaaccca atctcagctt tccagctata 37740 ctctcacccc atggaatttgcagatgaagt tcaaaaggac ctttgcatta tcctgcctcg 37800 ccctcttccc ccttcatttagacatcacct tcttctagaa cgtcttacct gacatgccct 37860 gctcccaacc cctgctgcccaattgtgtgc tctcccgtgt cctggcctgc catcctcttt 37920 agtaattgcc tgctccctcatctgtctccc cacccagaca ttaagctgaa tagactggat 37980 ttgtgtcttg tccatcactataatctcagc acctagtacc tagtaggtac ttaccatgta 38040 ttcattagca aaatgttatgtataaccttg caccttaaaa acaagagaag gaagacaaaa 38100 ttaagtctta agactatggtttagaacatg gatcagaaac tacagtctgc agcccaaatc 38160 cagaccaaat gaagagaccatgttcattta catacaacct atagcagctt tcacactaca 38220 ggagcagagc taagtagttccaagggaaca cacggccctg caaagcctaa aatatttact 38280 ctatagctct tcacagaaaaagttttcaga tccctcgttt agaactcttg ttcatatgca 38340 atttcactaa accatagttttttgggtttg tttggttttt tttggcaaaa aggaatgagc 38400 cgatccagaa aaggttgaaaagaatgaatc attactgctg aaagaatgtg cacacagtcc 38460 gtcagtattc tgctgccatgctgacaccca tccaatagtg tcatgagatg cagcagctac 38520 tactgtgttc tcaatgccgagtccacccac tccataacca tgtccaagca atcttgggaa 38580 catcatcacc atgcttgtttatccttaagg tattgcctca catacagcag tggctggtca 38640 taaagtcaaa tgacactagtggccaggagg tcaagagaat gagtgaggac aggtgggtag 38700 gcagcccagg ccctagcaacagcaggagct cacccctcag tcactctagc caggactgaa 38760 atacttttca ccctttcaagagagactagg aatctggatt tttatgtgaa atatcttgat 38820 tactaaatgt tgtcaacagacatgtcaaaa ggtaaaacta agtaagttca tggggcagat 38880 tgactattca ggttatagaattaaggattc ttatccaaca cagataccaa ccaaaaagct 38940 gacgtataac atattaggagaaactatgtg cactgtcgaa acatcaacaa ggggctaatg 39000 tctaaaatag tctatattggattccagttg aaacatgggg aaaggacatg aacaggcaac 39060 ttatgtcaat ggaaactcaaaaagataaca agcatatata aaagcattct caaattcagt 39120 agtaaacaga cagatgcaaataaaaagagg gaaactgctg ccgggcacag tggctcacac 39180 ctgtaatccc agcactttgggaggccgagg cgggcggatc atgaagtcag gagatcgaga 39240 ccatcctggc taacatggtgaaaccccgtc tctactgaaa acacaaaaaa ttagccaggc 39300 gtagtggtgg gcaccagtagtcccagctac tcaggaggtt gaggcaggag aatggcatga 39360 acccaggagg cggagattgcagtgagccga gaccatgcca ctgcactcca gcctgggcga 39420 ctgagtgaaa ctccatctcaaaaaatataa taataattat aattataata ataataaata 39480 gtaaataaat aaaaagagagagactgctaa agtctagaaa gttgaatgat gccaagcgca 39540 tgcaaagatc agggccttgggatggccggg tgcagtggct cacgcctgta atcccaccac 39600 tttgggaggc caaggcgggcggatcatgag gtcaagagat caagaccatc ctggccgaca 39660 cagtgaaacc cggtctctactaaaagtaca aaaaaatata tatatatata tatattatta 39720 tattatatat atatatatcagagccttggg aatccttgtg tgctgctggg gaaggtagtg 39780 gtgcagccac ccttgacagcaatctggcag tacttggtta tattaagtat aggcacacac 39840 cacgaccagg cagtcctactcctgggtcta aatcccaaag aattctcaca caagtccata 39900 aggagacatg tacgaggctcattcagcatt actgggagtg ggaatcaacc tgggtgtcca 39960 tctacaggag acgagatggacaaaatgtgg tggatattaa gaccagaatc accaagtaac 40020 agagatgggt ggtgagtgacaatcctaaga tacagaataa aggctagaac atgatgccat 40080 tcatgtaaat taaaaatagatgcacacaaa gcagtatacg cgtgaccctt gaatagcaca 40140 ggtttgaact gcctgtgtccacttacatgt ggattttctt ccacttctgc tacccccaag 40200 acagcaagac caacccctcttcttcctcct ccccctcagc ctactcaaca tgaagatgac 40260 aaggatgaag acttttatgataatccaatt ccaaggaact aatgaaaagt atattttctc 40320 ttccttatga ttttctttatctctagctta cattattcta agaatatggt acataataca 40380 catcacacgc aaaataaatgttaattgact gtttatatta tgggtaaggc ttccactcaa 40440 cagtaggctg tcagtagttaagttttggga gtcaaaagtt atacacagat tttcaactgt 40500 gcaggcaatc agttcccctgaccccctcat tgttcacggg tcaactgtat atacacaaaa 40560 gtattatatg aacctcattagaatagctgt ctatagggag aagagaatga gagtgggata 40620 aaacggaatg aacaaataaaccaacaaatg cattaacaag caaaacaaca gaggggcttg 40680 catgggccag tgatgataaagggctaagaa tgagaatata attaattcaa ttcctcacac 40740 ctgaggtcta aaaccaaggaaagggagggc caggcgtgga ggctcacgcc tgtaatccca 40800 gcactttggg aggctgaggcgggcggatca caagattagg agtttgagat cagcctggcc 40860 aacacagtga aagcccatctctacaaaaaa tacaagaatt acccaggtgt ggtggcacat 40920 gcctgtagtt agctactctggaggctgagg caggagaatc acttgaaccc aggaggcgga 40980 ggttgcaggg agccgagatcacaccattgc actccagcct gggtgacaga gtaagactct 41040 gtctcaaaaa aataaaaaaaataaaaaaac agagaaaggg aggaaactag atccaggctg 41100 actagataca gcctttagagttagaaaaga tgatttgaca atctaagccc acactcagat 41160 tgaatgaaat tgaaaagcctttcaaactaa aacatttaat tacaccatct gctgcagaca 41220 gaactcagac aactcaaacaggtaatgtca gcgtggtgtt ttatatcacc accctcaaca 41280 cagaataaaa atcagctgcatgtgaagcag tgactagaat gaagaaaagg ctgcttctta 41340 cttccttcta gtggttctttccgaaaacat taataggcac cagctctatg catgtcaccc 41400 tgcagggaga catggggtatataactatga cttactgttc attcctcaag gaattcccaa 41460 tcttgtggaa gattatacacaatgaggcaa caaaaactat ccaataaaac cacggaaaag 41520 aagccagtga caaagaagccagtgatgaaa ggccctgtga gcagagctga tggccatttg 41580 gggaagaaag accaacatggatgggggtga tcagggtggc tccgtgggaa agctggaaga 41640 gaagtggcag atctctgagctggatgatgg gccactacca tctgtatatg gctaattaaa 41700 gaccatgtgt ggattttttattcagctctt tcgtgtcatt cctgctatca gcacagaacc 41760 caatctcaac tttccagctatattgagcta aacttctcac ctcatggaat ttgcagataa 41820 agttcaaaag gatccttgccttttcaaaat aattttgaat ggttgagtag tccctctgtg 41880 ctctctcact gacaccctctcaaggctgct gagcacgtgc catgctatgg ctttctccaa 41940 catcaggaaa tgttctccactcagtttcac cttaatacaa atgtgttctc tcttcagaga 42000 aggcaaaaaa attcatgaccatctgactgg gagaagtcat ttctaggtaa agtgtccatc 42060 tttttctgag gaacacaggaggaaaatctt acagaaaaga gttaacacag caggcctaag 42120 actgcttttt aaaataaataaataaataaa taaataaata aataaataaa taaataaata 42180 aataaatgaa tgatagggtcttctgtattg gccaggctag tctcaaattc ctggcttcaa 42240 gagatcctcc caccttggtctcccacagtg ttgggattat agacatgagc cattgtgctt 42300 ggcccaagac tgttattcttaaaaagtctc ataaaaagca tggttaatcc ttggctggca 42360 cctgggaact tagatttcagaagggttccc accatccaac ctggaaagag ggactcactg 42420 tgcctaaatt attgtgtggtttatgctgaa ctcctgcttt tcttcaggta gcgtggaatg 42480 tggtatgtgc tgggcaaagggggcctgcat gaccagcccc caataaaaac cctgggtgtt 42540 gggtctctag tgagtttccctggtagacag catttcacat gcgttgtcac agctccttcc 42600 tcggggagtt aagcacatacatcctgtgtg actgcactgg gagaggatgc ttggaagctt 42660 gtgcctggct tcctttggacttggccccat gcacctttcc ctttgctgat tgtgctttgt 42720 atcctttcac tgtaataaattacagccgtg agtacaccac atgctgagtc ttccaagtga 42780 accaccagat ctgagcatggtcctgggggc ccccaacaca gaaataaatt ataaaagacc 42840 aaggactggg catggtggcccatgccggta atctcagcgc tttgggaggc cgaggcagga 42900 ggaccagtta agcccaaaagttcaaagtta cagtgaccta tgactgcgcc aatgcactct 42960 aacctgggag acagagcaagaccctgtccc caaaacaata aactaaacac atacttctgc 43020 cttccaagtg tcttaaaattcaatggaatg gtagaaacat ttttaaaaca ctaaatcaaa 43080 agaaacctgg aaaacaagagtgccgatggc caactaaaat gtctaggaaa tttctgaaaa 43140 gtaaaaagta ctcagaaccagattacctga gcaaaccata gcccaataca agcttgggag 43200 gaggctgtta tgcagaaggaaatggtaaca ggtttccagg aacagacttg taacagcaga 43260 tagaacagca gaggtagaacctgacaaggt gattacctgg ggaactgcag tctgaatgac 43320 caggactgtt ggacccttcccctcacatgg aatacacacg ccactcagca gcacaccaca 43380 gctcttcaac aatcacaggaggcacgctac gcctagtaag acaggaaaaa aggaattctc 43440 aaacttcgaa gatgaacacataaagaatca ccaagttttt attcagtatg atgaaacagg 43500 gacactgaat caacagaacacaaacccaag caaagataat tactagagca catagaagaa 43560 attattagat attcttgggaagacctaagg ggacattata aagagcaagc agttggtatg 43620 tgacgatctt tgtgatataccaagaaataa aaacacagga tgaagaccag atagagaata 43680 atgctactat ttgtgcaaaaaaggagaaat ggagaatctg attcatattt gcttgtattt 43740 gcatgaagaa actttggaaggtacataagt aactaacaac aatggttacc tacttgtaag 43800 gcgagagaag taagaggacaggaatggtgg gaacaccttt tgtgtccgga attggtgggt 43860 tcttggtctg acttggagaatgaagccgtg gaccctcgcg gtgagcgtaa cagttcttaa 43920 aggcggtgtg tctggagtttgttccttctg atgtttggat gtgttcggag tttcttcctt 43980 ctggtgggtt cgtagtctcgctgactcagg agtgaagctg cagaccttcg cggcgagtgt 44040 tacagctctt aagggggcgcatctagagtt gttcgttcct cctggtgagt tcgtggtctc 44100 gctagcttca ggagtgaagctgcagacctt cgaggtgtgt gttgcagctc atatagacag 44160 tgcagaccca aagagtgagcagtaataaga acgcattcca aacatcaaaa ggacaaacct 44220 tcagcagcgc ggaatgcgaccgcagcacgt taccactctt ggctcgggca gcctgctttt 44280 attctcttat ctggccacacccatatcctg ctgattggtc cattttacag agagccgact 44340 gctccatttt acagagaaccgattggtcca tttttcagag agctgattgg tccattttga 44400 cagagtgctg attggtgcgtttacaatccc tgagctagac acagggtgct gactggtgta 44460 tttacaatcc cttagctagacataaaggtt ctcaagtccc caccagactc aggagcccag 44520 ctggcttcac ccagtggatccggcatcagt gccacaggtg gagctgcctg ccagtcccgc 44580 gccctgcgcc cgcactcctcagccctctgg tggtcgatgg gactgggcgc cgtggagcag 44640 ggggtggtgc tgtcagggaggctcgggccg cacaggagcc caggaggtgg gggtggctca 44700 ggcatggcgg gccgcaggtcatgagcgctg ccccgcaggg aggcagctaa ggcccagcga 44760 gaaatcgggc acagcagctgctggcccagg tgctaagccc ctcactgcct ggggccgttg 44820 gggccggctg gccggccgctcccagtgcgg ggcccgccaa gcccacgccc accgggaact 44880 cacgctggcc cgcaagcaccgcgtacagcc ccggttcccg cccgcgcctc tccctccaca 44940 cctccctgca aagctgagggagctggctcc agccttggcc agcccagaaa ggggctccca 45000 cagtgcagcg gtgggctgaagggctcctca agcgcggcca gagtgggcac taaggctgag 45060 gaggcaccga gagcgagcgaggactgccag cacgctgtca cctctcactt tcatttatgc 45120 ctttttaata cagtctggttttgaacactg attatcttac ctattttttt tttttttttt 45180 tgagatggag tcgctctctgtcgcccagac tggagtgcag tggtgccatc ctggctcact 45240 gcaagctccg cctcccgggttcacaccatt ctcctgcctc aacctcctga gtagctggga 45300 ctacaggcaa tcgccaccacgcccagctaa ttttttattt tatttttttt ttagtagaag 45360 cggagtttca ccatgttagccagatggtct caatctcctg acctcgtgat ccatccgcct 45420 cggcctccca aagtgctgggattacagacg tgagccactg cgccctgcct atcttaccta 45480 tttcaaaagt taaactttaagaagtagaaa cccgtggcca ggcgtggtgg ctcacgcctg 45540 taaccccagc actttgggaggccgaggcgg gcggatcacg aggtcaggag atcgagatca 45600 tcctggttaa cacagtgaaaccccgtcgct actaaaaata caaaaaatta gccgggcgtg 45660 gtggtgggca ccggcagtcctcgctactgg ggaggctgag gcaggagaat ggcgtgaacc 45720 tgggaggcag agcttgcagtgagccgagat agtgccattg ccttccagcc tgggcgacag 45780 agcgagactc cacctcaaaaaaaaaaaaaa aaaatagaga cccggaaagt taaaaatatg 45840 ataatcaata tttaaaaacactcaagagat gggctaaaga gttgacggaa caaatctaaa 45900 tattagattg gtgacctgcaaaaccagccc aaggaacatc ccagaatgca gcccataaag 45960 ataaagagag catttccgctgggcacagtg gtatggcagg ggaattgcct gagtccaaga 46020 gttgcaggtc acattgaaccacaccattgc actccaggcc tgggcaacac agcaatactc 46080 tgtctcaaaa aaaaaaaaaattaaattaaa aaagacagaa tatttgagag aaaaaaatgc 46140 ttatttcaag aaacatgaaagataaatcaa gatattctaa ttcccaagta agaataattc 46200 cagaagcaga aaatagaatagaggcaagga aacactcaaa acttctccag tgccatagaa 46260 atgtgtatta atctttagaatgaaacggac taccaaatgc tgagcaggaa gaacaaaaga 46320 gatccactct taagccagtgtggtgcccaa gcgcagtggc tcatgcctgt aatcccagca 46380 ctttgggagg ccgaggcaggtggatcacct gaggtcagga gtttgagatc agtcaggcca 46440 acatggtgaa accctgtctgtactaaaaat acaaacatta gctgggtatg gtggtgcaca 46500 tctgtaatcc caactacttgggaggctaag gcaggagaat cacttgaaac caggaggtgg 46560 aggttgtagt gagccgagatcatgccacac tcccagcctg ggtgacagag caagattcca 46620 tctcaaaaaa aaaatccactcctagacaaa taatagttaa attttagaac accaaggaga 46680 aagaaaaaaa attgtaaagcttcagagaaa ataaacatta actacaaaga aacgagagtc 46740 agacgcgtgc acttcttcctagataccagc agataaagca atatctccaa aattcagaag 46800 gttttaacgt agaatcctatacccagtcaa gaatattcac atggaaaagt gaaataaaaa 46860 acattgttta aacatgcaagggttcagaaa gtttaccatt cacagaatcc ctgaaaacaa 46920 aaccaaataa tcacttaaggactcattaag aaaacaaatg aaataaaagc accaatgatg 46980 agtaaataat cagaaaaatttacagtttac ctaaataact gtttatgcat aatgtatgaa 47040 aacccaaaaa tttaatatgggacagaatta aaatcatgat aagattcttt tttgctttac 47100 tcatggagag ttcacataaacagattatct tttaatagca agagaaaaaa atgtttagat 47160 atgtgtgaaa aactaagggtaccaaaacag tgcaaattca tttatcatca ggaaaatcca 47220 aattaaaacc acagtatccaccagaataac taaaaggtaa aagacagaaa ttaccaagag 47280 ttggcaagaa tgtggagcaaccacatatac ttctggggta aataagttgg tgcaaccggt 47340 actgaaaact gtttgctagtatctactaaa accgagcaca tgcacagact acaaccaagc 47400 agttccactc ccagatacacactcaacaga aatgcacaca ctcactcaac aaaagacgtg 47460 tactagagtg ttcatgtacttactattcat aatagtccaa aaatgcaaac aaccaactgc 47520 caatcaaagt caaatgtatatctatattag ggatatatac aatggcatat acacagcaat 47580 gagaatgaaa tgaaccagctcggcacagtg gttcatgcct gtaatctcag cactttgggc 47640 gggtaaggca ggcagatcacttgaggtcag aaatttgaga ctagcctggc caacacggtt 47700 aaaacctgtc cccactaaaaacacaaaaat tagccgggca tagtggttgc aggcctgtaa 47760 ttccagctac tcgggaggctgggttgggag aatcgtttga acccgaaagc cggaggtcgc 47820 agtgagcgga gatcgtgccactgcactcca gcctggacga tagagcaaga ctccgtctca 47880 aaaaaggaaa tcaaaaatataaaataagat gacaggaata atccgcaaaa gatcagtaat 47940 caaaataaat ataaatgggctaaagctacc tattaaaaga caaagatttc acacccataa 48000 ggatagctac tatcaaaaaaagagagagaa taacagatgt tagcaaggat gtatggaaac 48060 tgaaattctc acgcattgctggtgagaata taaaatggtt cagcctctgc ggaaaacact 48120 atgctgggtc atcaaaaaattaaaaataga agtactactt gatccaacaa ttctacttct 48180 gggtatatac ccaaataactgaaagcaggg tcttgaagag atatttgtac acccatgatc 48240 atggcagcat tattcataatagctatgatg tggaaccaac ataaatatcc tttgataaat 48300 atatggataa gcaaaatgtggtgtatacat tcaatggaat attaattagc aataaaaatg 48360 aagaaaattc tgacacatgctacaacatgg atgaaccttg agggcattac attaaatgaa 48420 ataagccagt tataaaaagacaaatactat atgaggtact atattagata ctcatgcaag 48480 gtacctaaaa taggcaaattcatagagaca aaaagcagaa tggtggttgc caggggctgc 48540 ggtaatggat acagagcttcaattttgtaa gatgaaaaaa ttctggagat tggttgcata 48600 acaatgtgca cacacttaacactggggaac tgtaaactta aaagtagtaa atggtaaaaa 48660 taaaaataat aaataataaattttatgtta ttttaccaca atatttatta aaagacaaag 48720 attaactaat taaacaaaatccagccataa gctaatggta agagtaacaa ttaaagaaga 48780 cacagaaaat tgaaaatcagtgactagaaa aagatattcc atataaatgc taacaaaaag 48840 caagtacagc aatataaagagaatgaacaa aaaaaaaatt aaataagatg gctcgtttat 48900 tcccaaaagg tacaattcaccaagaagata caagaattgt gaacctttaa gcacataaaa 48960 cagcttcaaa aatacaacatttaaagaaaa atatatatta aacatagaaa tagtacaaaa 49020 acccctacaa gaatcataatgggagtcttc aatacaactc tccatatcaa caggtcaaac 49080 agagaaaaaa aataagttaaggatgcagaa aacctgaatt accatcaata aacttgagat 49140 taatatagaa ctgtatacccaatatactaa gagttcaggg aacagtcgtg actgacagtg 49200 gactgcaaat taatctgttcttaatctttg tttttctttc agcactgtgg cagaatagag 49260 atcctaaaaa ccttccagctacaaaacatc tttttaaaaa tataaaaaaa tacaaaaata 49320 actctgaaat caatagaagacacatggtga aaccaaaatt ctagaataca gggagaataa 49380 aggcattttc agatattacaaaaacagaaa attgatcatt gctgaagtaa tttctaaaga 49440 atgtacttga gggagaagaaaaatgttcca aagaaaagta tctgtgatac aagaaggaat 49500 ggaaagtgaa gaaatggtaaacaggtagat aaagctaata aatgttgacc tagaaaataa 49560 caaaaacaat agcaataatgtctcgttgga agggttgaag taaaaataca attaaggcca 49620 aatgtgaggt aagtggaatgaaagaattag aagtccttgc cttgttcaca ggactgatta 49680 aataaatgag ccaggttttccattcaaaca gttaaaactt gaacaaaata aactcaaatt 49740 aagtagaaag ataaaaaacagaaattaatg tcatagaaaa ataaaaaatc aatagaatta 49800 atcaataaat cctggttaataaaagctggt tctttgaaag gattaataaa ataatcatta 49860 agcaagtctg atcaaaaaaaaagagaaaag gtaccaaaaa aagtactgta tcagaaagag 49920 aacatacaga tacatacagatatgtaagag tctgttttct tacaccagaa tactatatac 49980 aacattatgc tagcatatattaaatttcaa taatgttaat gattttctag gaaaacagaa 50040 aatattaaat ttactttgaagaaacagaaa aactgagaaa aataaatgat catgaaaaaa 50100 atgaaaaggt aattaaatactgatattaac tgcctaaaca acaccagcag cagcccaggc 50160 agtctgcagt caagttctgccaaacttgag ggaacagata attcttctat tccagagcat 50220 agaaaatgat ggaaagtttcccaatttaat cagagaggac agcctgatcc ttgttatgaa 50280 cacagataaa aatggggtaaactatatgcc aaactcagat accaaaaccc taaataagat 50340 gctagcttat tgatgtgaacaatccaaaag tgcattttaa attagcccag ggttttagag 50400 aaagaaaatc tagcaatgtgaccaccactt atgttaacaa ttttaagacg aaaatctaca 50460 tgatcatatc aatgcatgctacacaaaagc atttgggcaa aaaacccaac acccaccctt 50520 gactttttaa actcttagtaattaggcata aacagaaatg tacttaatgt gatagaatac 50580 actcggtgaa gatacagagggaatgctccc taaaaccaag cccaagacaa agattcctat 50640 ttaacctcaa tagtcaacactgcagcgaga gtaatctatg gaagacaagg aaaaaagtaa 50700 aaacatgaga gacatctgttgtttaacaga caataagatc acctacttgg aagaggcaaa 50760 cgaatcaagc gaaaaactattaaaactgag acaggcttta gtatggaggc tcagcttcag 50820 ctgtagtttg ggctaccaaattcaactcgc ttgcttggag agttaatcct gcaaagctaa 50880 tttctgttga ggtattaggattgacaagcc tgtgctcctc cctcctcccc catcttcaac 50940 actgaaataa cacggtgtttggaactggat aacagaatct tccaaaaaca aaaattgtcc 51000 tgaagggctg acttgtgcccttactcaaaa aacactttat ctgctgcctg cagctcctac 51060 agttgctggt ggataagcctgccaaccagc tcggcgtaat tcttcctgca gagggcaagg 51120 aagagcactt tcacaggaaaatttttttcc gaactgtatg ccgcttatta cataaactta 51180 cgtgctggca aatggagctccagcaaaata agatattcag agtcaaactt ccttaggaaa 51240 aaaaaaaaaa aaaagcaagcacataacact aatttccttg catgggcact ggggaaggag 51300 gtcgttactt ccgcacgcccgcaggtccgc accaccggga aacccacggg caccgcgcgc 51360 tgcccccggg ccttccaggtgcactgcgcc gcggcgcccc agctgacccg ggatgcgcag 51420 ccctagccct tcccctgtcaccccggccag gaaggggcgg gagcgcggcg gacgccgagg 51480 gcgaagggct tctcggtcctctgcaccacg cagcaccccc aaggcacaac agggagggtg 51540 cgggaggctc ccgagacccaggagccgggg ccgggcgtgc ccgcgcacct gtcccactgc 51600 ggcgagggct ggggtcgcctccagggccgc agctgtcggg agccacctgg ctctcagtcc 51660 cgggtccctg cgacaaccctcgggcccgga ggggaggagg cggccacctg ccgctgccac 51720 ctgcggcacc ggtcccaccgctccgggccg ggcaggacag gccaggacgt ccctcctggg 51780 ctggggacag gacacgcgacgaggggaccg gggcccccgc ggcgaagacg cagcacgcct 51840 tcccagaaag gcagtcccgtgcccccacga cggactgccg gacccccgcg ctcgcccgcc 51900 catcccttca gaccacgcggctgaggcgca aagagccggc cggcgggcgg gctggcggcg 51960 cggctagtac tcaccggccccgctggctca gcgccgccgc aacccccagc ggccacggct 52020 ccgggcgctc actgatgctcaggagaggga cccgcgctcc gccggcgcct ccagccatcg 52080 ccgccagggg gcgagcgcgagccgcgcggg gctcgctggg agatgtagta cccggaccgc 52140 cgcctgcgcc gtcctccttcagccggcggc cgggggcccc ctctctccca gctctcagtg 52200 tctcatctcc ctatctgctcatcctctggt cgcacataat cgatgtttgg gcgtcccaag 52260 ccagatgtgg accccatttccgcactctac actggaggtt ttctaagggt ggtgcccgga 52320 ccagcagctt cagcctcatctgggaacttg agaaaatgca gattctccgt cccacccagc 52380 ctattcggtt tttcctgcactaaaaccatg aaggtggggc ccagcagtcc acattctcgc 52440 aagcccgtca agtgattctgaggcgccctc cagtttgaga gctatgctca cggcctcacc 52500 tccgccccgc aaggagcccggtcttgcctg tggcgctagc cgcacacgga cacctcatcc 52560 tgcggggccc gcccccccgctgcaccctca ccgcccaacg cctcctccgg gatgcagcgg 52620 aggcgcctgg aagtcggcaaggtcaacatc cccctcagca tcttccctac cctcacggct 52680 cctcctccag gggtgcctcatggccagggg ttagaaagag ccactgtgtt tcttgacatg 52740 gaagtggcct aagaccttaatgaaaactgc aggagtggaa tgacagaacc tttggtcata 52800 cttgagggcg tgaagctcaaatgaggagga aggaaaggat ccagggagaa taaccaaccc 52860 tggcaagttg tggcgcccaggtagaggggc gagcctaggc tagcggttct cgaccagggc 52920 cggtgttgcc cctcctcgccgccccgcgta catttgggga ggtctggaga catttttggt 52980 tgtcatgatg cgggagttgctactgttgcc taagtgggta gacacgaggg tgctcctcaa 53040 catcctacct gaaggacaggactgccccac aaggaagaat gatccggccc caaataagaa 53100 accctgggct ggtcagcaacaacccctttg ttctgagaag agaggaggaa agaataaaag 53160 aagtggggtg aagttttggtttggtagagg aaacttgaag acattttcac tggaaaggaa 53220 gagaggaaga ggagggagatgtctgtaagg acgagcaaac cgggtgacag ctgatttcct 53280 catattgaag taatgagtcctagttataat aaattcctaa taaaaaccca gtttatccct 53340 gcaataaact tgtcttttttttttaaatat actgcttgat tctgtttgct aatattttat 53400 ttacaggctt tgcattgatatgcaaaaatg agatgggcaa taattttctt tttgaatgtc 53460 taatgttgtt tggtttcagaatcaatgtta tgctcacatc ataaaaaatt tggaaccgag 53520 gcaggaggag tgcttgaggccagaagttcg agaccagtct aggaaacaca gtgagacccc 53580 cccatctcta caaaaaaaaaaaaagaaaaa aaaatgggca tgtttgcttt ttccttttac 53640 tctgaacaat ttaaggagcattaaaattat ctattctttg aggtttgatc atttcccagt 53700 taaaaatgtt cctcccagcctgatgctttc tttggggagg gtaaatcttt taaggctaga 53760 aaagtttctt ctgtggcaattttattattt acattttaaa aattattcta gagttaattt 53820 tgataaagca tgtatttcttaaaacaaatt atcctttttt tccagatgtt caagtgtatt 53880 tgcataaagt tgaggaaagtagtcttttgt gaatctttta acttctccca aatatcttat 53940 tttgtgtatt tttgcttctttattttgtta acttttaaaa gtgtattttt ttttcaaaga 54000 atcagctctt aggtttatgtttttggttat actggagctt ttttcttctt ctttttaaaa 54060 tattttttct cctttattttttagacgtat tttgatctaa cgtaatcgga agaaggtaaa 54120 ttagaatctt ttgttactattgtgttttta tttctcctta tttctctgaa gtcctgcttt 54180 ataaatagta ccatgttatttgtgcataaa tattcatttg tcttatattc ttgggaattt 54240 tcccacttca tcataaaatgaccttccttg tctcatttaa tgtgttcaaa ctttgccctg 54300 aatttaactt tgtctgatattttaccatcc tgctgaattt tgtttgttac cccaaacaac 54360 ctttgctgtt ttcgtcttttctgaaccctt tattttaggt aatcccttga attagagcac 54420 taagttttgc tttgtgattaaatctgaaaa tctttatctt gccatagatg agttgagccc 54480 tattcatgtg acagctatattatgctgttt catagccctt ttggtccttt tttcactctt 54540 gcattgcata ttttgtgtttattgtgtttt gtgtttcttc tgataatttg gaaggtttgt 54600 atttttattc agggagttgccttataatca tactccgcaa tacacatcgt cctcagtttc 54660 ttcagactgt ctgttaactccctattctga ataaaaatga cattgtaatt tccctctttt 54720 ttctttaccc cttttcttctcctcacctaa tgtaaatgat tttatccttc tttagtattt 54780 gcttttttaa ttaactacatttataaatat ctttatcact tgatttttaa atcagctttg 54840 aatgagatat ttggattcctagatataaaa gatgttaatt ataccatttc cacgttagta 54900 ggtttataaa atcatacattctgctgtgta accataatcc cacgtttgtt ttagttccac 54960 tcctacagtt aaaagattcagaagtattat taacagttat tttgccatag ttttttcccc 55020 aacccatttt gtggtaagttatgatcctgc tttagtttct taagaataat ttatagagca 55080 gagtgtggtg gctcacgtttgtaatcccag cactttggga gacaagaggt agaaggatcg 55140 cttgaagcca gcagttcaagaccaccctga gcaacatagt gagaccttgt ctctacaaaa 55200 aattttaaaa tttagccagacgtagtggcg tgtgcctata gtcccagcta ctcaggaggc 55260 tgaggcaaga ggattgctagagcccagaag tttgaggctg cagtgacctc tgattgtgcc 55320 actgcacccc agtctgggcaagaaagtgag aacctatctc tttaaaataa caataataac 55380 ttatgaaaat tatattccctgagtttttca tgtttaaaaa tatttgttgc ctttatcctg 55440 taaaagtttg agtataaattcttgggttat actttattta ttgaagaatg tataagtatt 55500 gtcttctaga attgagtgttgctgtaatga aaccagaagt cagcctggtt tatttttcct 55560 cagaaatgag gtaattgccggccggacacc gtggctcatg cctgtaatcc caacactttg 55620 ggaggccgag acaggtggatcacgaggtca ggagattgag accatcctgg ctaacatggt 55680 gaaaccccgg ctctactaaaagtacaaaaa gttagctggg catggtggtg gacgcctgta 55740 atcccagcta cccgggaggctgaggcagga gaatggcgtg aacctgggag gaggagcttg 55800 cagagagctg agatcgcgccactgcactcc agcctgggcg acagagtgag actccgtctc 55860 aaaaaaacaa aaaaaaaacaaagaagtgaa gtaattgcca tgatgctcca agaattatct 55920 ctttgtctat gaaatccagaaatctcactg ttatacattt tggaattatt attctgggcc 55980 aatatttcct gggacacaatagattgactc tatagattta attttttttt tttttttgag 56040 acagagtctc actgcaatctcagcttactg caacctctgc ctcacgggtt caagcaattc 56100 tcctgcctca gcctcccaagtagctgggac tacaggcgcg tggcaccatg cctggctaat 56160 ttttgtcttt ttagtagagacagggtttca ccatgttggc caggctggtc ttgaacgcct 56220 aacctcaagt gatccacctgcctcagcctc ccaaagtgct gggattacag gcgtgagcca 56280 ccatgcccag cctcaattcctctttctatc tggtaatttt tctgaagttg aaaacatttg 56340 ttctaatacg ttatttcagtgttcttctaa gatgtgtaaa gcaccctatt cccaggtcag 56400 cccccatctt gctagtgagctcggctggtt cttcacaaga gctctggttt tctcctgctt 56460 aatctcaagt acctctgtcagcctccacct ggtttatgat ttggagtttt ttggtttttg 56520 ttttttgttt ttgacagagtcttactctgt cacccaggct ggagagcagt ggcataatct 56580 cagctcactg caacctctgtctcccaggtt tgagcgattc tcctgcctca gcctactgag 56640 tagctgggat tacaggcgcgtgccaccaca cccggctaat ttttgtattt ttagtagaga 56700 tggggtttca ccatgttggccagggtggtc ttgaactcct gacctcaggt aatccacctg 56760 cctcagcctc ccaaagtgctgagattacag gcgtgagcca ccgcgcctgg catggtttgg 56820 agttttaatc tgtagttttaataaagatag tgcttatgtt tgtgtttctt atatttcttg 56880 gtactcttgg gtaatttgtaagatccccat atctacacaa gaagtccatt ttcaattctt 56940 ttcttcagac tgtttattttattttatttt attttatttt tatgtttgag atggagtctc 57000 gctgtgtcac ttctggaggctggagtgcag tggcgcgatc tcaggtcact gcaacctccg 57060 tctcccgggt tcaagcaattctcctgcctc agcctcccga gtagctggga ttacaggcac 57120 ctgccacttt ttaatttttttagagacaga gtctcgcttt gttgaccagg ctggagtgcg 57180 gtggtgcaat catggctgactataacctcc aaatcctggg ctcaagtgat cctcctgcct 57240 cagcctcctg agtagctgggactacaggca catgccacca tgcccagtta attttaattt 57300 ttttgtagag acagggtctccatatgttgc ccaggctggc ctcctactcc tggcctcaag 57360 taatcctcct acctcagcctcccaaattac taggattata agcatgagcc accatgccca 57420 gccttgttct actactttaatttcatatgt taggtgacca tgtaattgat catccaaacc 57480 aggatactgt aagaatgaaagaggctgaca gtagtatgat gctgggacta gcattgtgca 57540 ctgagattat ttctgggaaagcaggagata cggtcaccct acttatagtg tgcttgtctt 57600 tggattgttg aatttggagtttctatttgc aggcttattt caactgggca gccttgatcc 57660 gccctgccca gcaatgctaccgttctctcc accgggtctc tgggacccct tcagtcacta 57720 tacttagctc agttccccaccctcccactc cctaaaagcg taaccaggaa tcctgcctca 57780 ggtctactgc cgtcttccgtgggctgtttc agttcctatt acccagagtc aaactcccag 57840 cattccctac ctgattccagacttggagtc cagagcttta acctcttcag gccaactccc 57900 cactttgcat ttctgtccctatatcttagt ccatggagat acatttcatg tctttgagtc 57960 tacttacaaa gtaaattttgctgtttttta attttttttt tgagatggag tcttgccctg 58020 tcacccaggc tgtggtgcaatgacgccatc tcggctcact gcaacctccg cctcctgggt 58080 tcaagcgatt catctgcctcagcctcccaa gtagctgtga ttacagacag gcaccaccac 58140 gcccagctaa ttttttttatcttttagtag agacagggtt tcaccatgtt ggccaggctg 58200 gtcttgaatt cctgacctcgtgatctgccc atctcggcct cccaaagtgc tgagattaca 58260 ggcgtgagcc actgtgcccagccaattttg ctttttttat atttcattgc tatatgttta 58320 gaggataagt ttacagtgctatatgcattc ccaaatatta gaccaaaaaa atctccaaaa 58380 aattagaaag aaaatccaaaaaatctcaaa aaataccaaa aagcaacaat ctcacagacc 58440 atactcactg acccccaataaaataaaatt agaaattaac cacaacttaa caaaataaag 58500 tactcaagtc agagaggaaagaggaaataa acatcaaaat tacaaagtct aggcggtggc 58560 tcacgcctgt aatcccagcactttgggagg ccaaggcggg cagatcacaa ggtcaggaat 58620 tcgagaccag cctggccaatatggtgaaac cccgtttcca ctaaaaatac aaaaattagc 58680 caggcatagt gatgtgtgcctgtaatccag ccacttggga ggctgaggca ggagaatcac 58740 tgaacccagg gagacgaagattgcagtgag ccaaaatcgt gccactgcac ttcggcctgg 58800 gtgacaaagc gagactccatctcaaaaaaa aaaaaattac aaactcttta gatagaaatt 58860 ttggtgtttt tttttgagacggagtctcac tctgtcgcag aggctggagt gcagtgggac 58920 tatgtcagct caccgcaacctccatctcct ggattcaagc aattctcctg tctcagcctc 58980 ccaagtagct aggattacaggcgcccacca ccagacccag ctagttttta tatttttagt 59040 agagatggtg tttcaccatgttggccaggc tggtctcaaa ctcctgacct caagtgatcc 59100 acctgcttca gcctcccaaagtgctcagat tacaggcgtg agccaccgca ccccacctag 59160 atagaaattt caacatgaggccgggcacaa tggctcacgc ctgtaatctc agcacttcag 59220 gaggctgagg cgtgggaggatcacttgggc ccaggagttc aggaccagca tgggtgacag 59280 agacagaccc tgtctctatttatttgaaaa aaaaaaaaaa aaagagagag agaaagaaat 59340 ttcaacatga aaagtatctctcaaaccctt cgagatgttg gcaaaaagcg actcaaagga 59400 aaatgtatta ctgtgtgtgaatttgcttga aaataagaaa gaggccgggt gtggtggcta 59460 acacctgtaa tcccaacactctgggagtcc gaatcaagtg gatcatgagg tcaggagatc 59520 gagaccatcc tggctaacatggtgaaaccc tgtctctact aaaaatacaa aaaattagct 59580 aggcgcggtg gctcatgcctgtaatcccag cactttggga ggctgaggca ggtggatcac 59640 ctgaggtcag gggtttgagaccagcctggc ctacatggtg aaacctcgtc tcttctacaa 59700 atacaaaaat tagctgggcgtggtggtggg tgcctgtaat cccagctact cagaggctga 59760 ggcaggagaa tcgcttgaacccgggaggcg gaggttgcgg tgagccgaga tcgcaccact 59820 acactccagc ctgggcaacagcctgggtga cacagtgaga ctccatctca aaaaatacaa 59880 aaaattagct gggtgtggtggcctgcgcct gtagtcccag ctacccggga ggctgaggca 59940 ggagaatgga gtgaacctgggaggaggagc ttgcagtgag ccgagatccc accactgcac 60000 tccagcctgg gcgacagagcaagactcttg tctcaaaaaa aagaaaaaaa aaggaaaaaa 60060 gaaccctgat aataaagaaaccaaatgttc aactctcaaa gctcggacac tttaaagaaa 60120 taattaataa aggcagaagttaaagggagg atgataaagc aatttttttt gttggttttt 60180 ttgagatgga gtcttgctctgtcacccagg ctggagtgca gtgatgcgat cttggctcac 60240 tgcaacctct gcctcccgggttcaagcaat tctcctgcct cagcctcctg agtagctggt 60300 actacaggtg cgcgccacctggcccagcta atttttgtat ttttattaga gacggggttt 60360 caccatattt gttaggctggtctcaaactc ctgatctcag gtaatctgcc cacctcggcc 60420 tctcaaagtg ctgggattacaggcaggcgc caccgcgcct ggcctaaagc aaaatattgg 60480 ttctgtgcaa aaggtcaataaaaagagcaa acgtttacaa actggagcca gcacccattc 60540 agctcagtgt gtctggagaaaaaacaatct cgcttcagaa ttcatgatta cgcagccctt 60600 tttgcttcct aaaaatcctactatgttgct gttgaccatt ctctctcttt ctctctctct 60660 tgctttctct ccagaaaagctattcagaca ttctcctctt tcctcaaacc tccaacactt 60720 cctcctccat ccttagcctcagctgctgac ctcacttcta atcattgaga aaccaggaga 60780 agcatttaag agtgaacctccgcctccccg cacgggcaaa accacccacc cacagaattg 60840 tgccccaatt ctgcgtcctctcctctcacc atggatggac ggtccaggct ccgagccaaa 60900 gccaggcctc ccctggagctctggatccac cacctgcagc ttctcaggca gggccccagc 60960 agctcccctg ctcccttgtaccatcaatcc ctcccctcac tgggtcactc ccaacaatat 61020 atatatttag tgatgtttctcccatgtggt aaaatcactt agcctctctc ctcccccagc 61080 tactatccta tttgtttctttccattctct gcaaaacttc tcaaagcatt gtgtctatgt 61140 gctgactcca tttatcttctcccgttctct gctgagtcct tcccacagac tctcacccca 61200 gttactccat gaaatgacctctgcactgcc acatccaatg gtgaatgttc agttcttaat 61260 tttattcagt ctttcagcagcatttgacct ggccgatcac tccctcttct taaaaatact 61320 tttctcagcc aggcgtgatggctcacacct gtaatcccaa cactttggga ggccaaggcg 61380 ggaggatcat gagagcccaggagttcaaga tcagcctggg caacatggca agaccctatc 61440 tctacaaaaa ctaaaaagtagccagtgtga tggcatgcac ctgtagtccc atctacttag 61500 gaggctgagg cagtaggatgacttgagcct gggaaatcaa ggctgcagtg agccatgatt 61560 gcaccactgc actccagcctgagtgacagc gagaccctgt ctcaaaaaga caaaatagga 61620 aacttttctc agcatattcctctgattctc ctgctgcttc tgtctgcaca gattcagtct 61680 cctttgccgg ttcttcctcatcctcctgat ctcttgacct tgaagtgccc cagagtacag 61740 tctttttttt tttttttgagacgcagtctc gtctgtcacc caagctggag tgcaatggcg 61800 aggtctcagc tcatgcaacctctgcctcct gggttcaagc gattctcctg cctcagcctc 61860 ccaagtagcc aggactacaggcacatgcca ccatgcccag caaattgttg tatttttagt 61920 agagacaggg ttttactatattggccacgc tggtctcaaa ctcctgaact cgtgaaccac 61980 ccgcctcggc ctcccaaagtgctgagatta caggcatgag ccaccacacc cggcccagag 62040 tacagtcttt agacggcctctctacctata cttgctcccc tcataaactc ctcctgcctc 62100 atggctttaa ataccatcggtagactgatg actcccatat ttctcttttt tttttggaga 62160 cggagtctcg ctcagtcccccaggctggag tgcagtggcg cgatctcggc tcactgcaag 62220 ctccacctgc caagttcacaccattctcct acctcagcct ctccagtagc tgggactaca 62280 ggcacccgcc accacgcctggctaattttt ttgtattttt agtagagatg gggtttcacc 62340 atgttagcca ggatggtctcgatctcctga cctcgtgatc cgcccatctc ggcctcccaa 62400 agtgctggga ttataggtgtgagccaccgt gcccagccga tgactcccat atttctatct 62460 cttgctgtgt gggagttctcctcagaactc catactcata aatccaactc tcataaatag 62520 tatctcaaat gggcaatatgctcaaaagtc aattcctact tttctcccta aacttgcttt 62580 cctgcagtct ccaccatcttaatgtccaat ctaacattag gaggcaaaaa ctttgaagtc 62640 attcttgact cttctctattacacacccta tccaatcttt ctgcagatcc agtcgacccc 62700 caaatccagt tagctctcatcatctcccct gttaccccct ggtccaggcc atcttcctct 62760 ctcacctgaa tcactgcagcattctcctca ctggtctctt tggttctgtt ttcactccac 62820 cttagcatag tctccacagagcagtcagag ggatcctttt aaagtgtaat tcccatcctg 62880 tccctgctct gctcaaaaccctgtcgtgat tcccgtttta atctgtcaga ttaaaagcca 62940 gagtctttcc agtgacctacatgatctgcc tattatcacc tcccacttct ttccccttgc 63000 tcactccact ccagctctgcagctgtcctt tctgtttcct gaacagccca gattttgctt 63060 ctttagaacc tttgtatttgctgtcccctc tgtctggaat gtttttccag gaagtcacct 63120 ggctctctcc tgcacttccttcctgaccac catgtttaaa aatcactcaa acacacttca 63180 ggccggacat ggtggctcacgcctgtaatc ccagcacttt gggaggccaa ggtgggtgga 63240 tcacctgagg tcaggagttcgagaccagcc tggccaacat ggtgaaactt cgtctctact 63300 acaaatacaa atagtagccaggtgtagtgg cacacacctg taatctcagc tactcaggag 63360 gctgaggcag gagaatcgcttgaacccaga aggcagagga ggtgcagtga gccaagatca 63420 cgccacaaca ccccagcctgggtgacagag caagacccca tctcaaaaaa aaaaaaagaa 63480 aaaaaaatca cacaaacacacttctcttca tattcctttt ccaagtttta tttttctcca 63540 gaatacttta cattgttttaatggaagttc tccgtttccc cccaactaga atggatactt 63600 cctgcaggta ggcactctagtcctcccatc caagtactaa ccaggctcaa ccctgcttag 63660 cttctgagag caggggagatcaggcctgtt cagggtggta tggcccagga attttgattc 63720 tgttttattc attgctgttctgttgattct cttttgttcc tcctcctagt gctgagaaca 63780 ctacttgtac ataataagcattcaataaat atttgttgaa tgaatgactt gttgaatgaa 63840 ttaatctcag aaatgcaggactggttctac attagaaaat ttttcaaggt cattctctgt 63900 tgtcgtaaca cattaagagaggaaaatttt gtactctaaa tcatttgata aaatacatac 63960 tgatttctgt tttcaaaaactcttagtggc tgggcgaggt ggctcacatc tataatccca 64020 gcattttggg aggacgaggtgggcggatca cttgaggtca ggagtttgag accagcctgg 64080 ccatcatggt gaaaccctatctctactgaa aatagaaaaa ttagccgggt gtggtggcgc 64140 atgcctgtag tcccagctacctgggaggct gaggcaggag aatggcttga acccgggagg 64200 cggaggttgc agtgagccaagatcatgcca ttgcactcca gcctgggtaa cagagtgaga 64260 ctccatctca aaagaaaactcttagtgagt ttaggaatcc aaggaagacc ctcaaactaa 64320 atagataatc tagctaccagaagccttcag taaaccttaa cactccatgg tgaaacatta 64380 gaaacattcc tactaaaagacaggctaaga atgcctgcaa tcttcacggc tagtccaaga 64440 agtcaaaaag aagaaatgagcgctgattta aaaaaataaa caaacaaaaa actaccgatg 64500 cagaggctgg cagcaaggactgaaggactg tacagtactt gcctggagca ggcggatggc 64560 cacacccctg cgaagcctgctcagctggct gggggacgct ccagtgtgtg agtggcagga 64620 tgcagggtac ttcctctgccagggagttgc actggggaga tcctccccca ctcacacttt 64680 ggcagctggg gctttggaatgtgacttagc ttctgtcaaa gggtcaatcc accctttgat 64740 atatgatgca aaggcgaacatatgatgcaa aggtgagaga acagcccaaa ttaggacttt 64800 taccacagct gtggaggtggacagcgacag tggtgggccc tggccagact tttcatgctc 64860 aaaggtggtg gttgttcttcctacttcttg tccctccagg gcttcctttg cctgtgtgct 64920 gaacctgctt cttttaattttttttaactt ttttaaattt ttaattgttt taattaaaac 64980 aaattttgaa aactgtctgaacctgctttt gaaccctgct atgatttgaa tgtttgtccc 65040 ctgccaaact gattttgaaacttaatctcc aaagtggcaa tattgagatg gggctttaag 65100 cagtgactgg atcatgagagctctgacctc atgagtggat taatggatta atgagttgtc 65160 atgggagtgg catcagtggctttataagag gaagaattaa gacctgagct agcatggtcg 65220 ccccttcacc atttgatatcttacactgcc taggggctct gcagagagtc cccaccaaca 65280 agaaggctct caccagatacagctcctcaa ccttgtactt ctcagcctct gtaactgtaa 65340 gaaataaatg ccttttctttatgaattacc cagtttcaga tattctgtta taaacaatag 65400 aaaacgaact aaggcaaactctcatgattc tactgccatg ccattccaat aaactccctt 65460 tatgcttaag agagccagagttggccaggc gtggtgactc acgcctgtaa ttccagcact 65520 ttgggaggcc gaggcaggtggatcacaagg tcaggagatc gagaccatcc tggctaacac 65580 ggtgaaaccc cgtctctactaaaaatacaa aaaaattagc tgggcgtggt agtgggtgcc 65640 tgtagtccca gctactcgggaggctgaagc aggaggagaa tggcgtggac ccaggaggcg 65700 gagcttgcag tgagtcgagatcgtgccact gcactccagc ctgggtgaca gaatgagact 65760 ccgtctcaaa aaaaaagagagccagagttt atttctgttg cttgcaacca agaaatctgg 65820 ctggtgcact gaagtttccataaataatag caatttaaag actctttcca agccaggcaa 65880 tgcctagcct tgtgtagtccttgtggtaat acattcattc attcatttgt tcaaccaact 65940 gtgctccaga gactaagaatacaaaaatgg gggccgggtg tggtggctca cacctataat 66000 cctagcactt tgggaggccgaggcaggtag atcacctgag gtcaggagtt cgagaccaac 66060 ctggccaaaa tggtgaaacccctactctac taaaaataca aaaaattagc tgggggtggt 66120 ggcggacacc tgtaatcccagctactcgtg agactgaggc aggagaatca cttgaacccg 66180 ggaggcagag gttgcagtgagccgagatcg caccactgca ctccagcctg ggcaacaaga 66240 gcgaaactcc acctcgaaaaaaaaaaaaaa aaaaaaagag ggccggggct gggcgcagtg 66300 gctcacgcct gtaatcccagcactctggga ggccaaggca ggagaattac gaggtcagca 66360 gatcgagacc agcctgaccaacatggtgaa accccatctc tactaaaaat acaaaaatta 66420 tccgggcgtg gtggcgcacacctctagtcc cagctacttg ggaggctgag gcaggagaat 66480 cgcttgaacc cgggaggcagaggttgcagt gagccgaaat catgccactg cactccagcc 66540 tgggtgacag agtgagactccgtctcaaaa aaaaaataaa aaaaaaaaaa gaattcaaaa 66600 attgtagagt tatagtgtgcttctagttta gttgagagga catctgtcct tcaaggaagg 66660 ctagaatcta taccctgagtccttactgaa atcaatccag cagtcaaaac atgggaccaa 66720 cgatcacagc agtaagataggaagagcacc tttgtacatt tagctcatgt tgagataagc 66780 cactgacaga gctgaaggaagctcacagtt ctgggttcca tcctttggca tttaaaaaga 66840 aaagtgctaa gaaaattcggttggtcacgg tggctcacgc ctgtaatccc aacactttga 66900 gaggccaagg caggcagatcacgaggtcag gagttcgaaa ccagcctggc caacatggtg 66960 aaaccccgtc tctactaaaaacagaaaaat tagccgggca tggtggcgca tgcctataat 67020 cccagctact caggaggctgaggcaggaga attgcttgaa cccgggaggg ggaggttgca 67080 gcgagtgaga gcaggccactgcactccagc ctgggagaca gagcaagact ctgtctcaaa 67140 aaaaaaaaag aaaaaaagaaagaaaggaaa aaaagaaaga aaaaaaaaga aaaaagaaaa 67200 ttcaggccag gccaggcctggtggctcaca cctgtaatcc caacactttg ggaggctgaa 67260 gcgagacggt gccttagcccaggagtttga gaccagcctg agcaacatag cgagaccctg 67320 tctctataaa aaaaaatttttttttggcca gacgcagtgg ctcacgcctg taatcccagc 67380 actttgggag gccgaggcaggtggatcacg aggtcaggag atggagacca tcctggctaa 67440 cacggtgaaa ccccatctctactaaaaaat acaaaaaatt aaccgggcgt ggtggcgggc 67500 gcctgtagtc ccagctactcgggaggctga ggcaggagaa tggcgtgaac ccgggaggcg 67560 gagcttgcag tgagccgagattgcgccact gcactccaga ctgggagaga gtgagactcc 67620 gtctcaaaaa aaaaaaaaaaaaaaaaaaat taattgtcag gtgtgctggc atgcagctgt 67680 agtcctagct actcgggaggctgaggtaag aagatcgctt gagcccagga gttcaaggct 67740 gcagtaatag tgcctctcactctaccctgg gtgacaatga gaccctctct caaaaagaaa 67800 gaaaaaaggg aaagaagaaaagaaagaaag aaagagaaga aaggaaggaa gaaagaaaga 67860 aaaagaaaag gaaggaaggaagaagaaaaa aaaagaaaga aagaaaagag agagaagttc 67920 aaagaccaaa gggtcaggatcccaaaatag tttttatgtt ttatttattt atttacttat 67980 ttatttttga gacagtatggctctgtcgcc caggctggag tgcagtgatg cgattgcggc 68040 tcactgcagc ctccaaactgggctcaggtg gccctcccac ctcagcctcc cgagtagctg 68100 ggaccacagg cgcgtgccaccatgcccagc taatttttta attctttgta gagatgaggt 68160 ctctatatgc tgcccaggctggtctcgagc tcctgggctt aagccatcca cccgcctggg 68220 cctcccaaag tgctgggattacagaagtga gccaccgcgc ctaatcgggt ggtttgtttg 68280 tttattgacg gggtctcgctgctgcccagg ctggagtgcc agtggctgtt cacaggtgca 68340 gtcctggagc attgcatcagctcttgggct ctagcgatcc tccagagtag ctgcagctgg 68400 gattccaggc gcgccaccgcgcggggctca gaatgggttt ttatattgag ggttatgctg 68460 ccacctagag gatatatgtagtaccgaact gtgtgcgcag ggaggctgag gttgcagtga 68520 gccaagatga tgccagggcactccagcgtg ggtgacagag caagatttca tctcaaaaaa 68580 aaaaaaaaaa aaaaaaaaaaaagaattgaa agtaaggtct tgaagagata tttgtgcctg 68640 tatggtcata gcagtattaactttgaccca ctagctaaaa cacaaaagca acatgtgtct 68700 gtcagcaggt gaacggataaacaaaatgtg gtatatatgt acaattgaat attattcagc 68760 ctttaaaaag gaataaaaggctggatgcgg gggctcacgc ctgtaatcct aacactttgg 68820 gagactgagg tgggtggatcacccgaggtt aggagtttga gaacagcctg gccaacatgg 68880 tgaaacttca tctctactaaaaatactaaa attagccggg catggtggca cttgtctgta 68940 atccaagcta ctggggaggctaaggcagga gaattgcttg aactcaggag ccggaggttg 69000 cagtgagcta agatggcaccactgcactcc agcctgggca acagagtgag actccatctc 69060 aaaacaaaca aacaaaaaattattatttcc aaagaaacaa gaccctgggt ccatttccca 69120 gcccacacct gatgttgactcacaacacac agcctggttt gctatgagcc tgcttcattt 69180 aattgtcacc ttaacttcacatcaccctca agtcctggaa taactctttg ctgacctttg 69240 tgtgctgagc catctccatgtcgctcaacg tgcagtccct ctcactgcac tgagtcaata 69300 gccagacgtg gtctgactgcagggtcatcc ttggtggctt aggctgactc gggcatagca 69360 gggtgctctg agacctcaccgcatataggc tttgccccca ataaactcta tataatattc 69420 atattatgtg gtctgggtgtgtgtagcttt gcactgtctt ctcgtgacag tgccctcaac 69480 ctctttccca ggatttcctcctctacctcc tcaagtccca ctgctctgca aagaccaaaa 69540 gctgcagagt cccagctccctcctttacac cccacgacgc agcctcctct ctcagaaccc 69600 tttaaacaga gtcttttactgcagatccca agaacagcca cacccctctc tcccacccac 69660 tccagacaca cccaggtaattatagcaccc agggtaacta tgtagatgga gtccctggaa 69720 catgtggata gtgccccctgggagtatgca aaagcaacat tgctggcacc tgcagagaac 69780 agggtgacat ccaggaatcagagcatgggc ctctgggagg tagggatgtg gccaggcagg 69840 ctgccaaaaa ttggtagagcaaggccacag gatctttctg accttccttc caaacagagg 69900 ctcctgtact ggtgatccctgtgttgattg accactccct tcctgggggt cgtggtctct 69960 gtcccagttg cccggacttctgtgagtgtc ctactgaggt ccttttcatg agaagcatgc 70020 tgtccttcca cctgctgggagcaagagtga caacttcaat actataatag cagtggcata 70080 cagagaagaa gaaagatgaagtggcaagaa aaacaggctt ccaagcagga gtttttctat 70140 aaaaacaaaa acgtttacaagcaaactttt tataaagggc tagatagtaa atattttagg 70200 ctttgagagc cacatagacttgtttgcagg gactcaatgt cgctattgta gtttgaaagc 70260 agccatcagg gttatgtaaatgagtgagtc tgattttgtt tcagcaaaat tttatttacc 70320 aaaacagaca atgagtgggctggatttggc ccatgatcct tagtttgcca actcctgctt 70380 tgggctcacc cagatctgattttgaattct ggctctgcta ctggttagct gcaggagctt 70440 ggaaggctct ctgagcctgtttcctcatct gtaaaattaa agcaataatt tctaacactc 70500 aagagtgtta cctcacgcctgtaatcccag cactttggag gctgaggcag gcggatcacc 70560 tgaggtcaga agttcaagaccagcgtggcc aacgtggcaa aaccctgtct ctactaaaaa 70620 atacaaaaag tagccgggcatggtggcgcg catctgtaat cccagctact tgggaggctg 70680 aggcagggat actgctagaacctgggaggt ggagcgtgca gtgagtggag atcacacctc 70740 cacactccag cctggccgacagagcgagac tccatctcaa aaaaaaaaaa aaaaagagtg 70800 ttagaaggtt ttgagataatgaataaaaga tgccttgtgt atactaagta ttcaacaact 70860 gatagctgca ttggtctaattataacagtt tagaagcgat tgagtcaaca aatgctggat 70920 ttgtcaggga ggacttcctatcaggaggta gatcttgggc tgagtcctga agcaaagata 70980 ggcattggat agaggagttgagagaacacc ctaggactgt tattattatt attcgacacg 71040 gagtctcttg ctctgtcacccaggctggag tgcagtggcg cgatctcggc tcactgcaac 71100 ctctgcctcc caggttcaagcgattctcct gcctcctaag tagctgagac tacaggtgtg 71160 tgccaccaca cccggctaatttttatattt ttagtagaga cagagtttca ccatgttggc 71220 catgctggtc tcgaactcctgacttcaggt gatccacccg cctcagcctc ccaaagtgct 71280 ggaataacag atgtgagccaccgcacccag cccagaacca tttttcaatc cttggctctg 71340 ccttttatta gctgcaagatctcaggcaat ttatttaacc tctccaaaga ctcattttct 71400 cattcacaaa atgaggcaaataataatatc tactatccca ggttgtcatg agaattaaat 71460 gcaacatgac atttaatgaaatgagaagtc ccttggacat taactggcta aagtatgtgc 71520 tcgacaagga tatcattttaggtggatact tagcatctca gaactgatgc tcacaatgga 71580 atatcattga aacgcattaaaattcatttt aaatgattgt aggtagtgag gcaattgaaa 71640 gaagaagaca agaggactgattataatgct tcaggctcac tagtctcctt ttaggaggga 71700 aaaacaattt caagttaaattttaggctct agatttttac ccctgctgct cattagaatc 71760 acccagattg atgaaatcagagcccatctg aggctgtgtt tttcatctcc agaatgagag 71820 ctgttgtggg gattaagtttttgaaaaagt acatctaaca ggtgatcgaa aatgatagtg 71880 atattattgc agtgatggtcattattgttg ttattattat actgaaagag gcttcagttt 71940 tctgatccat aaagtgagggaattgcatga gaccattgct aagattcctt ctagctctgt 72000 ttttttgttt ttgttttttagacagagtct ctgtcgccca ggctggagtg caatggcatg 72060 atcttggctc actgcaacctccgcctcccg ggttcaaatg atcctcctgt ctcagcctcc 72120 gaagtagctg ggactacaggcacacaccac catgcccagc taacttttat atttttaata 72180 gaggtggggt ttcaccatattggtcaggct ggtctcaaac tcctgacctc aggtgatcca 72240 cccgcctcgg cctcccaacatgctgggatt acaggcatga gccactgtgc ccaacccctt 72300 ctagctttct tgatcactgattctagggtt ctctgctgaa atatatttga gacatcctgg 72360 ataaaagatc atgcaagagctcccaatatg gtattaataa ttgattctgg aggcttagct 72420 actcctgatg gattagacatgactcaactg cctctcttat gtgtacaaca caacaacaca 72480 accaagaaag gttattctggcattccattt attcagttta tttacagccc ttacttccag 72540 cagcacgtta aagatatggccagggccggg tgcagtggct caagtctgta atcccaggac 72600 tttgggaggc caaggtgggcggatcacaag gtcaggagtt tgagaatctg gcaattcttc 72660 agacttagaa gcaaccagctcgataacaca gtcttgtgtg ggctctccct ctgtccctcc 72720 ctcgcttccc tcatttctcatccctgcccc tgagactgtg caccttcaca tagccctgcc 72780 atgagacctt catctcaggctttgctttct ggggtaactg aggctaaaca ctgagtggcc 72840 ctaaaagagg attgggatttggaagttaga ttattcacca gagaacagac tttgctgatg 72900 atcaggccca ggttgtaattgttgaaaaaa agagaggatg catagtctta tctcatctcc 72960 tagtcaaagt caacaccatgataaataaga gtcaaatcct gagatgtgaa ttggggacat 73020 ttgagtggtt aaccctgagaagcttgcacc ttcagacccc tcaatacccc tgctccccag 73080 agaaggctgg acattgacctcagcacaggc aggagccctg caagatgcca tttgtcctac 73140 taaagatgga cccctccactctgtttctag gtaaataacc aaagtcaagt ctccacacag 73200 cctgagcaag aaagtcagagcctgctacag gagaaaatac cacactggcc aaaggattca 73260 ctagccctgg ccactgtgtgtgggaggaac cagggaatca tgtgtgggag tcaatgttga 73320 agctgttgga ctgggggtggggtggaatat aagcctggcc ctggggagtt tttcccgttt 73380 gagggccttt acccacaactcaagatccag tgctatagca ggagatccca gagctagtcc 73440 taacagatgg tcaggattgaacttggccta gagtaaaatg aggaggatag tgccagaact 73500 ttctcaacat actattgaggaagaggtcag aaggcttaag gaggtagtgt aactggaaag 73560 gggtcctgat ccagaccccaggagagggtt cttggacctt gcataagaaa gagttcgaga 73620 cgagtccacc cagtaaagtgaaagcaattt tattaaagaa gaaacagaaa aatggctact 73680 ccatagagca gcgacatgggctgcttaact gagtgttctt atgattattt cttgattcta 73740 tgctaaacaa agggtggattatttgtgagg tttccaggaa aggggcaggg atttcccaga 73800 actgatggat ccccccacttttagaccata tagagtaact tcctgacgtt gccatggcgt 73860 ttgtaaactg tcatggccctggagggaatg tcttttagca tgttaatgta ttataatgtg 73920 tataatgagc agtgaggacggccagaggtc gctttcatca ccatcttggt tttggtgggt 73980 tttggccggc ttctttatcacatcctgttt tatgagcagg gtctttatga cctataactt 74040 ctcctgccga cctcctatctcctcctgtga ctaagaatgc agcctagcag gtctcagcct 74100 cattttacca tggagtcgctctgattccaa tgcctctgac agcaggaatg ttggaattga 74160 attactatgc aagacctgagaagccattgg aggacacagc cttcattagg acactggcat 74220 ctgtgacagg ctgggtggtggtaattgtct gttggccagt gtggactgtg ggagatgcta 74280 ctactgtaag atatgacaaggtttctcttc aaacaggctg atccgcttct tattctctaa 74340 ttccaagtac caccccccgcctttcttctc cttttccttc tttctgattt tactacatgc 74400 ccaggcatgc tacggccccagctcacattc ctttccttat ttaaaaatgg actggggctg 74460 ggcgcggtgg ctcatgcctgtaatcccagc actttgggag gccgaggcgg gcggatcatg 74520 aggtcaggag atcgagaccatcctggctaa cacggtgaaa ccccgtctct actaaaaatg 74580 caaaaacatt agccaggcgtggttgcaggt gcctgcagtc ccagcggctc aggaggctga 74640 ggcaggagaa tggcgtgaacctgggaggtg gaggttgcaa tgagccgaga ttgtgccact 74700 gcactccagc ctgggtgacagagcgagact ccgtctcaaa aaaaaaaaaa aaaaaaaaaa 74760 tagctgggca tggtggcgcgtgcctgtaat accagctact ctggaggctg aggcaagaga 74820 atcgcttgaa cccagtaggcggaagttgca gtgagccgag atcttgacac tgcactccag 74880 cctggtgaca gagtgagactctgtctcaaa aaaaaaaaaa agaaaaaaaa agacagaaag 74940 aaagagcaca gacagagtcacaggtatttg cagtaggaag ctgtcaggtt agagtgcacg 75000 gaaatagaaa gtatattttacacttacagc acatcttcgt ttgattagcc acatttaaaa 75060 tactgaatag caacgtgtggctatttagta ttcactaaaa tcttggacag tgcaagtcta 75120 aagaatcctt gatccgtccggcatggtggc tcacgccttt aatcccagca ctttgggagg 75180 ccaaggtgga aggatcacttaaggtcagga gttcgagacc agcctggcca acatggtgaa 75240 acctcgtctc tactaataatacaaaaaaaa ttagccgggc atggtggtgc atgcctgtaa 75300 tcccaggtac ttgggaggctgaggcaggag aatagcttga atccaggagg cgctgcagtg 75360 agccgagatc atgccatgccactactgcac tccagcctgg gcaacagagt gagactgtct 75420 caaaaaaaaa aaaaaaattgttgggcgtgg tggctcacgc ctgtaatccc agcactttgg 75480 gaggctgagg ggggtggatcacctgggttc tggagttcga gaccagcctg gccaacatgg 75540 tgaaacccca tctctactaaaaatacaaaa attagctggg cgtggtggtg ggcacctgaa 75600 atctcagcta ctcaggaggctgaggcagga gaatttcttg aacccaggag gcagaggttg 75660 cagtgagcca agatcgcgcctctgcactcc atcctgggtg gcagagcaag actatgtctc 75720 aaaaaaaaaa aaaaaaatacttgattgtct ggacattctg cagaacatca tatggagaca 75780 ctatgttgac gacatcatgctgattgtaag caagaaatgg caagtgttcc agaaacacag 75840 tcaagacaca tacatgccagaaggtgagat ataaactcta ctaagattca gtggcctgcc 75900 acactggtga catttttaaacctgctagat gtttgtgtag aaaaggattt aaccttgccc 75960 aaagaggggt ctggcctttgtccccagcta ctggacataa tctctttaaa ctcttgaaat 76020 atcattcctg atagaagtatttttgttttg actaggggcc ttgggccagc cagatagcaa 76080 caatgtgatc tgggttgggggctttggatc aggtggcatc agtgtgacct cctgagtggc 76140 tagagactag aatcaaccacatgggcagac aacccagctt acatgatgga attccaataa 76200 agactttgga cacaagggcttgggtaagct ttcctggttg gcaatgctct atactgggaa 76260 acccattctg actccatagggagaggacaa ctggatattc tcatttggta cctccctggg 76320 ctttgcccta tgcatttttcccttgtctga ttattattat tattatgaga tggaatctcg 76380 ctctgtcacc caggctggagtgcagtggaa tgatctcaac tcactgcaac ctctgcctcc 76440 ccggttcaag cgattttcctgtctcggcct cccgagtagc tgggactaca gatgcatacc 76500 accacacccg gctaatttttttgtattttt agtagagacg gggtttcacg ttagccagga 76560 tggtctcgat ctcctgacctcatgttccgc ctgcctcggc ctctcaaagt gctaggaata 76620 catgtgtgag ccaccgcgcccagccccctt ggctgattat taaagtgtat ccttgagctg 76680 tagtaaatta taaccgtgaatataacagct tttagtgagt tttgtgagca cttctagcaa 76740 attatcaaac ctaaggatagccttggggac ccctgaactt gcagttggtg tcagaaataa 76800 gggtgctcat gtgtgtaccatgccctctaa ttttgtagtt aattaacttt cacaacttta 76860 ttattaccgc ttacactcaatgtttattca catttatcca cataccactt attctagtgc 76920 cttgcatcaa agactttctatctcatgtac tttattctgc ttgaagtaaa tcctttagga 76980 tattcttttt tttttttaaactttgcacat acatactttt attttttatt tatttttaat 77040 tttgttattt ttgtgggtacgtagtagata tatgtattta tggagtacat gagatgtttt 77100 gatacaggca tgcaatgtgaaataagcaca tcatggagaa tggggtatcc atcctctcaa 77160 gcaatttatc cttcaagttacaaacaatcc aattacactc tttaagttat tttaaaatgt 77220 acatttaatt ttgtattgactagagtcact ctgttgtgct atcaaatata attttttttt 77280 tttttgagac agagtctcactcagtggccc agactgaaag tgcagtggca caagctcggc 77340 tcacttcaat ctctgcctccctggttcaag cgaatctcct gcctcagcct cccacatagc 77400 tgggattaca ggcacacaccaccatgccca gctaattttt atattttttt agtagagacg 77460 ggttttcgcc atgttggccaggctggtctt gaactcctgg cctcaaatga tctgaccacc 77520 tcagcctccc aaagtgctaggattacaggc atgagccacc acacctggcc aaaatagaat 77580 attctttagt gaggtctgctggtgacaatt tttttctttt ttttgagact gagtctcgct 77640 gttgtcagct tgggctggagtgcaatagca cgatctcagc tcactgcaac ctccacctcc 77700 cggattccag caattctcctgcctcagcct cccaagtagc tgagagatta caggcaccca 77760 ccaccacacg cggctaatttttgtattttt agtagaaatg ggggttcacc gtgttggcca 77820 ggctggtctc gaactcctgacctcaggtga tccacccacc ttggcctccc aaagtgctgg 77880 gattacaagc atgagccaccacgcacagcc aattttttcc gtttttgtct gaaatcttat 77940 tttgtgtcat ctttgaaatatatttttgat ggatataaaa ttgttggttg atagttatta 78000 tcattattat tattattttgagacagggtc tcactctgtt gcctatgctg gggtgtagta 78060 atgtgatctc ggttcactgcagacttgacc tcctagggct caggtgatct tcccacctca 78120 gcctccctag tagctgggactacagatgca tgccaccata cccaactaat ttttctattt 78180 tttgtagaga tgaggctttgccacatttcc caggctggtc tctaactcct gagctctagc 78240 aatccaccca ccttggccttacaaagtgct gggccatgac tagccagcag ttacttttta 78300 tagcatattg aatatttaatatgaatcttc tggcatccac tgtaactgtt taaaaaatca 78360 gctgtttact tggcactctttttttttttt ttttttttga gacagagtct tgccctgtcg 78420 cccaggctgg agtgcagtggcgtgatcttg gctcactgca agctctgcct cccgggttca 78480 cgccattctc ctgcctcagcctccggagta gctgggacta aaggcgcccg ccaccacgcc 78540 cggctgattt ttttgtatttttcgtagagt tggggtttca ccgtgttagc caggatggtc 78600 tcgatctcct gacctcgtgatctgtccgcc tcggcctccc aaagtgctgg gattataggc 78660 gtgagccacc gcgcccagcctctttttttt ttttttttag acggagtctt actctgtcat 78720 ctaggctggt gtacagtggcgtgatctcag ctcagtgcaa cctccacctc ctgcctcagc 78780 ctgccaaata gctgggattacaggtgcgta ccatcacgcc cggctaattt ttgtattttc 78840 agtagagatg gggtttcaccatgttagaca ggctggtctc gaactcctgg cctcaagtga 78900 tctgcctgcc ccagcctcccaaagattaca ggcatgagcc accgcacccg gccaagtagc 78960 actcctttga aggtaatctgcttcccctac ccctagcaat ttttaacaat ttttcttcat 79020 ttttatttcc tgaagttttgttattaataa tctgtgtgca gatttctttg tatttctttt 79080 gtttgcagtt catagtgattcttgaattag tgtgttggtt tctgttatca ccacaggaaa 79140 attgtcagcc gttagcttttcaaatatttc cttgctaaat tctctcttct cccctttcgg 79200 tacaattgat ttgattaaaactaaaaccag ggccgggtgc agtgactcat gcctgtaatc 79260 ccaacacttt gagaggctgaggcaggtgga tcacctaagc tcaggagttc aagaccagcc 79320 tggccaatat ggtgaaaccccgtctctact aaaaatacaa aaattaccag gcatggtggc 79380 acacatttgt agtcaggaggctgaggcagg agaattgctt gaatccagga ggtggaggtt 79440 gcagtgagct gagatcccaccactgcagtc tggcctgggc gacagagtga gatgagaatc 79500 tgtctcgaaa aaaaaagttatgaatgtttg ataaactata tttgttagaa tgtttgttgt 79560 agaatactat tcattgatttttaaacaatg ttagattaaa ccattcactg gatttgtgat 79620 aattaactta ctgattttacctcactgatt tgttgtaatt aatacaactg gtataaaaag 79680 actgtgacga ggccgggcatggtggctccc gcctataatc ccagcacttt gggaggctga 79740 ggcaggcgga tcacctgaggtcaggagttc aagaccagcc tgaccaacat ggtgaaaccc 79800 catctttact aaaaatacaaaattagccgg tcgtggtggt gcatgcctgt aatcccagct 79860 cttcgggagg ctgtggcaggagaatcactt gaacccggga ggtggaggtt gcagtgagcc 79920 gatatcgcgc cattgcactccagcctgggc aacaagagcg aaactccgtc taaaaaaaaa 79980 aaagaaaaaa aacacataaaacaaaacaac actgtgacgg ttcccaaaaa ttaggagcat 80040 aattaaagga actcctgataaaaattaatt ttatcttaca tgtaaactaa aatgacttta 80100 tgaagttaat tcagaaatacaatgcagggt attagtttgc cacagctgcg tattcagcct 80160 aatgtaatat tcttgttatttttaaattct tcttttaact ttactcatat gtggatcatc 80220 aaatttcaaa agattaaatgacaatactct tagcagcaag cttccctaag catataaaca 80280 ttttaatggg tgatgattcagaaggtaccc gaagaatatg tactgccaga tatcattcac 80340 ccccatatac ctgcccgacagacatcccat tttgggaccc tggataaatg tgtgggtgga 80400 gagaaagata ggagaaagtggtataagcaa atggctttgg agtctgattg acagcgattg 80460 aaatcctgtc tctacctcttaacagcctca tgatcctaca taagttaccc cgatcctcag 80520 ggccacatct gtaaattgggggttgcgatg gcagccatct cacagggtct cttttcgggg 80580 aagggcagga attatggattaagtgagcta gtaattgtaa agcacttaat acaaggaggg 80640 cgcataataa gtacttcataaataatgacg gccattatca tgactgaggt gtatgcagct 80700 gtcggggatt acggcgacttcagaatttct ggtgggcagg gctcaaaggc agcaaatcac 80760 actggaagtc gaggtgaggcactgcttctg cacagactgc ttagctggag agaatgagga 80820 aggcttagag gagatttagaggaacttaga gtcctccgcc tccaactctg tgggatctgc 80880 tcccgtgcca gagacattcaggggatttct cgcactctcc cctcccctac gtccctcccg 80940 ccccatccaa ctaaccacacaacacataca aaatagcccc tgcgaggttc tgcacgctgg 81000 aagggaacag gagaagggcgctgcgctttc ttgctgatgc cctgtacttg ggcccctggt 81060 agacacagcc acttgtcccctcagcctgca gagaaatccc acgtagaccg cgcccgggtc 81120 cttggcttca gccaatctccctttggtggg ggtgggatgc acgatccaag gttttattgg 81180 ctacagacag cggggtgtggtccgccaaga acacagattg gctcccgagg gcatctcgga 81240 tccctggtgg ggcgccgctcagcctcccgg tgcaggcccg gccgaggcca ggaggaagcg 81300 gccagaccgc gtccattcggcgccagctca ctccggacgt ccggagcctc tgccagcgct 81360 gcttccgtcc agtgcgcctggacgcgctgt ccttaactgg agaaaggctt caccttgaaa 81420 tccaggcttc atccctagttagcgtgtgac cttgagcagt tgactttatt tttcagtgcc 81480 tagttttcca gataccaggactgactccaa ggactattac tcatctggag ggtttagcac 81540 agtaccgtcg catagtaaatttccatgtca gttttggtta cctttcatgc acttgcaaac 81600 atgccatgct ctgaaacgaaataggcacat cttttttttt ttttttttta aggagtcttc 81660 ctctcgccca ggctggagtgcagtggcgcg atcttggctc actgcaacct ccacctcccg 81720 tgttcgagat tctcctgcctcagcctcctg attagctggg actacaggca tgccacgacg 81780 cccagttaat ttttgtatttttagtagaga cggggtttcg ccatcttggc caggctggtc 81840 taactcctga cctcaggtgatctgactgcc tcagcctctc aaagtgttgg gattacaggc 81900 ataagccact gcatctggccagaaatgaaa taagtaaatc ttttaacctg ctctaacaat 81960 atagtgaaaa gaccatattattattagagc aggttaaggg atttgcctat ttcgggttct 82020 agttatagtc ttaaacttggacattcttgt agaaagtaaa aagtttcctc ttcaaagttc 82080 cccttcttgt taaagaatacatcataagtg ttagaagtaa tagtttattt taaagactaa 82140 ctttcttcaa gcctccttgctttgtgctaa taactctttg ttaagcccta tcctatgtaa 82200 ctgttggaca tgctcacaggcacgttccag ttcacagcct atgccccttc cttatttgga 82260 aatgttattg cttccttaaacctttcggta agcaacttcc tctccttctt cgttcttcct 82320 tgcacttacc tatttagaaagttttaggct attagcaaat cggctatcag tttaagagtg 82380 tgaggtcccg ctccagccaatggatgcagg acatagcagt gaggacgacc caaatgcgta 82440 agggataaat atgtttgcttttcctttgtt caggtgtgct ctcgacatcg ttccatctgc 82500 gattgagcac cctttctgcagaaagtaaag attgccttgc tggagatctt ttgtctccgt 82560 gctgactttt cttcgtggcaccgattatct atttctaaca attttggtat ttctaacatt 82620 ctgaacaatc ttgggctagttgtctcttct gggcctgttt ccccatccgt cacatgataa 82680 acttcattgg tttaaaaaccccagcgaaca tttattgagt tactattacc ttcctgccct 82740 ccccaacccc aaccccagggagcagttaca acctcagccg ctgagcgcac tcgccgggtg 82800 ttaagaagca ccaaagacagggaggcttga ttgattttgc tttgggagta gagggtcaga 82860 agattcacag gaaaatggcatttgagcaag gatgattcac tggagctagc ttttaaatac 82920 tggcgaggct tttatgttgcagtcccttac aaagttgagc attcgcaggg actgcactcc 82980 gaaataagcc cgcttccccttttcattcgc taatgatcca gggagctgct ggttccgcat 83040 gcggcaggtt gtgccttttcctaatcaggg ttctgcatcg cctcgaaccc gcaggccgtg 83100 gcgggttctc ctgaggaagcagggactggg gtgcagggtg aagctgctcg tgccggccag 83160 cgcctgtgag caaaactcaaacggaggagc aggaggggtc gagctggagc gtggcagggt 83220 tgaccctgcc ttttagaagggcacaatttg aagggtaccc aggggccgga agccggggac 83280 ctaaggcccg ccccgttccagctgctggga gggctcccgc cccagggagt tagttttgca 83340 gagactgggt ctgcagcgctccaccggggg ccggcgacag acgccacaaa acagctgcag 83400 gaacggtggc tcgctccaggcacccagggc ccgggaaaga ggcgcgggta gcacgcgcgg 83460 gtcacgtggg cgatgcgggcgtgcgcccct gcacccgcgg gagggggatg gggaaaaggg 83520 gcggggccgg cgcttgacctcccgtgaagc ctagcgcggg gaaggaccgg aactccgggc 83580 gggcggcttg ttgataatatggcggctgga gctgcctggg catcccgagg aggcggtggg 83640 gcccactccc ggaagaagggtcccttttcg cgctagtgca gcggcccctc tggacccgga 83700 agtccgggcc ggttgctgaatgaggggagc cgggccctcc ccgcgccagt ccccccgcac 83760 cctccgtccc gacccgggccccgccatgtc cttcttccgg cggaaaggta gctgaggggg 83820 cgccggcggg gagtcaggccgggcctcagg ggcggcggtg gggcaggtgg gcctgcgagg 83880 gctttcccca aggcggcagcaaggccttca gcgagcctcg acctcggcgc agatgccccc 83940 tgagtgcctt gctctgctccgggactcttc tgggagggag aaggtggcct tcttgcgcga 84000 ggtcagagga gtattgtcgcgctggttcag aagcgattgc taaagcccat agaagttcct 84060 gcctgtttgg ttaagaacagttcttaggtg ggggttagtt tttttgtgtt tctttgagga 84120 ccgtggatca agatcaaggaaatctcttta gaaccttatt atggaagtct gaagtttcca 84180 aatgttgagg gttttatgtctaaaagcaac acgtgaaaaa attgttttct tcacccagtg 84240 ctgtcttcca atttcctctttggggggagg ggtagttact gctgttacta aaataaaatt 84300 acttattgct aaagttccccaacaggaaga ccactacttt tgatgacttt ggcaagtttg 84360 ctaactactg gaaccctaacttacaaacga actacttaca tttttgattt ccagttgtat 84420 tacctgccca atgtttacgtagaaacagct taattttgat tctgggtaac gttgttgcac 84480 ttcattaaaa atacatatccgaagtgagca agtatgggtc tgtggacagc agtgattttt 84540 cctgtcaatt cctgttgcttcagataaaat gtaccagaca gaggccgggc gcggtggctc 84600 acgcctgtaa tcccagcactttgggaggct tggcgggtgg atcacctgag atcgggagtt 84660 caagaccagc ctgaccaacatggagaaacc ccgtgtctac taaaaataca aaattagcca 84720 gggtggtggc gcatgcctgtaatgccagct acttgggagg ctgaagcagg agaatcgctt 84780 gaacctggga ggcggaggttgcggtgagcc gagatagcac cattgcactc cagcctgggc 84840 aaaaagagcg aaactccgtctcaaaaaaaa agtaccagac agaaatgggt tttgttttct 84900 ttttttgttt tgagacggagtttcgctctt gttgcccagg ctcgagtgca atggcgcgat 84960 ctcagtctcg gctcactgcaacctctgtct cccaggttta atcgattctc ctgcctcagc 85020 ctcccaagta gctgggattacccatgcccc accatgcccg gctaattttt gtatttttag 85080 tagaaacggg gcttcaccatgttaggctgg tcttgaaccc ctgacctcaa gtgggcctcc 85140 cacctcggcc tcccaaagtgccaggattac aggcatgagc caccgcggcc agccagaaat 85200 gggttttgga aaaagcactaaacaaaatcg aacttggttt catatgacag ctctgctgct 85260 aactgtaaca ggggcagaccagttaaccta cttttctgtc ttctgtcagc tgagaattag 85320 atgattccca aaggcccattgaactctgaa tgactttaaa tacttcttct taagtgggta 85380 cacggttttg gtaactgatgccaggtgatg aatgcatgaa agtgcttaat gaatgaaacc 85440 ggtaaaatag taggaggaagctttattggt aaggcagggg tatacctaat agctctctaa 85500 tttattggta ttgaagtggttaacttttgt ttttttaagg ggggaaaaca ttctaagaat 85560 aatgaggcaa actgcatattgcacaagaga ctgttgtctc tattcaacaa ataccttttg 85620 agtgtccaga gtctgccaggtgctgtgcta ggccctcacg attgagtagt gaaccagaga 85680 atgtccctgc acccatggagcttattgtct actggggtag acagataata aataagcaaa 85740 caaatcttct ctcttctccctttcgctcca tgtaagtgtg tgtgtatagg tgtatactta 85800 caagttgagt aaagtgttatgaaagattaa gaggagaaat gcattttggt tagatgttag 85860 aggactcagc aggtgaccttgaaacttaga gctgaaggat cagtaggagg taactagaga 85920 ggccagggaa tcgcatgttcaaaggccagg aggcaagaaa gagcatggtg cccttcaaga 85980 gaggaaagaa ggctactgtgactggagcat agatgtaggc aagtgttggg tgattgagag 86040 ctctacgggc catggttaggttttattcct aatgccgaga tgccaaacat ggtggttcat 86100 atctgtaatc ccagtattttaggaggccga ggcaggaata tagcttgaac ccaggagttc 86160 aagaccagcc tgagcaacatgagacctgta caaaacattt aaaaaattgc tgggtatgat 86220 ggtgcacacc tgtggtcccagctactcagg aggctgaggc agaaggatca cttgagccta 86280 ggaggtggag gctacaatgagccatatttg agtcactaca ctccagcctg gatgacaaag 86340 tgagaccatg tgtcaaacaaaatacagaaa gaatattaat ttaaaatttt gaaagaggag 86400 tgatctgaac ttatatcttaaaaagatcat tctagggcat ggtggctcat gcctgtaatc 86460 aagggctttg ggaggctgagacaggaggat cacctgaggc cagttcgaga tcaacctgta 86520 cagcatagag agactccatctctacaaaaa gaaaaaataa atagctgggt gttgtgagtt 86580 attcaggagg ctgaagcagaaagatcactt gagcccagga gtttgaggct gcagtaagct 86640 atgatcccac cactgcaacacagtgagatc ttgtctcaaa aaaaaaaaaa aatcattcta 86700 ggtgcttttt ggaggctggatgtggtaaga gtagaagctg gagatggtcc tgttagggat 86760 tcgattcaga ctttaaataccatcaatgca ttgagtccca aatttacatc actacgttgg 86820 atccttgccc ctgaatccagactggtatat ccaactttag gttcagtttg tatctctacc 86880 tgaccaatat agaggtgtccagtcttttgg cttccctagg ccacattgga agaagaattg 86940 tcttgagcca cacatagagtacactaacgc taacaatagc agatgagcta aaaaaaaatc 87000 gcaaaactta taatgttttaagaaagttta cgaatttgtg ttgggcacat tcagagccat 87060 cctgggccgc gggatggacaagcttaatcc agtagatacc ttcaacttac aatatctaaa 87120 attttatgcc agatttagtcattttaaacc tgctcatcag tttttctcaa gaagtagtat 87180 tttggctttt tttcttttcttttttttgag atggagtttc gctcttatcg ttcaagctgg 87240 agtgcagtgg cggatcttggctcactgcaa cctccgcctc ctgggttcaa gtgattctcc 87300 tgcctcagcc tcgcaagtagctggaattac aggcatgcgc caccatgacc agctaatttt 87360 tggagacagg gtttcaccatgttggtcagg ctggttttgt actcctgacc tcaggtgatc 87420 tgcctgcctc ggcctcccaaaggctgggat tacaggcatg agccaccgct cccggctgca 87480 tttttggatt tttagttgctcagcccaaaa ctttagtaca tctttgaacc tcttctttcc 87540 tcctactcta tatctgatccatcagcaaat ctgttaggtc tacctcacac atatcgaaat 87600 cctaccacgt ctcaccatctgtgacaatta acaccctggt ctaggcagtc atctctgtta 87660 agattgagtg gttaaggatgtcctctaagg agatgacatt caaatcttag cttaaatgtc 87720 aagagggagc tggttttataaagattgagg aggcagcatt attttgccat aggcttccat 87780 ttggtttcca ttccattcttgatacttatg gtatatattc aaaacaaatg cacagaaaca 87840 gacccaggta tattgggaatttcggatata gagttcctag ttgggaaaag atagactgat 87900 ctgtaaatga tgctagttatccatcatctg gcaaaaaata atttcctgcc tcctctcata 87960 tatctcagat caacagactttttctgttaa gggccaaatc ataaatattt taggctttcc 88020 agaccatatg gtttctgtcacactctcctt tatccttgaa gccatagaca atatgtaaac 88080 aaatgggcat ggctgtgctacgataaaact ttacttacaa aaactggtag tgggccagtt 88140 taggcatggc cagcactttgggaggctaag gcagatggat cacttggggt caggagtttg 88200 agaccagcct ggccaacatggtgaaaccct gtctctacta aaaatacaaa aaatagctgg 88260 gcatggtggt gggtgtctataattccagct actctggagg ctaagacaca agaatcactt 88320 gaacccagga ggcagaggttgcagtgagct gagatagcac cactgcactc cagccagggt 88380 gacggagtct taaagcaaaacaaaacaaaa ggtagtgggt tgtatttggc ccatgggctg 88440 tagtttgcca atccctgatgcagaaacaaa ttccaggtaa ataagagcct ggaatgttaa 88500 aaaaacaaaa cttgaagtcatgtagaagaa caggtagggg gaacaatcct gatctcagga 88560 taggaaggga tattgcttaaaataagacac aggaaaatat aatccatgtt gtgtaaattt 88620 gactacgtta aaacttaaaactttcgccaa gcgcggtggc tcacgcctgt aataccagta 88680 ctttgggagg ccgaggtgagcagatcacca ggtcaggaga ttgagaccat cctggctaac 88740 acggtgaaac cccgtctctactaaaaatac aaaacattag ccgggcgtgg tggcgggcgc 88800 ctgtagtccc agctacttgggaggctgagg caggagaatg gcctgaaccc gggaggcgaa 88860 gcttgcagtg agctgagatcgcgccactgc actccagcct gggcgacaga gtgagattcc 88920 gtctcaaaaa aacaaaacaaaacaaagcaa aaaacctaaa actttcatac aataaagtat 88980 acctaagata cttctagaagagaagattta catccaggac gtgtatggaa tttctgcaag 89040 taataagtaa aagacaagggacatgaagag gcagttcaca aaagaggaag ccaaaatgac 89100 caataaacat gaaaggatgtttaacctcaa aggaaacaag gaaatgaatt aaaaacatca 89160 aatgccattt caaaactagtaagttggcaa aattaaaaat accaaggatg agaatatgaa 89220 gcatggctat atgagtgcatggaatggtac agtcactttc attaaaaatg cacataattt 89280 gttttttatt tatttttttgagacagtcta tgtcgcccag gctagaatgc agtggcatga 89340 tctcggctca ccacaatctctgcctcctgg gttcaagcaa ttctcctgcc tcagcctcct 89400 gagtagctgg gattacaggcacatgccaca acgcccggtt aagttttgta tttttagtag 89460 agacagggtt ttgccatgttggccaggctg gtctcgaact cctgacctca ggtgagctgc 89520 ttcccaaagt gctgggattagaggcgtgag ccaatgctcc tggctgaaaa aaatgcacat 89580 aatttgttac ctagcaattccatgtctaga ggcttatcct agagaaattc ttgcttatat 89640 gcataggaag acgtgtactagaatgttcac tagttgaatg tttaagtgaa aattaggaaa 89700 taaagtaaat gttcattaacaggaaaatga gtaaaggtat atttataaaa caattaagta 89760 gctaaaatga ataaactagagctgcgtgaa tgaactagaa ctggttcaat agtcatgtca 89820 gattattgaa tgaatacaggtcagatatgt atagagtgtc atttgtgtaa ttaatttttt 89880 tttttttttt gagatggagtctcactctgt tgcccaggct ggagtgcagt ggcgtgatct 89940 cagctcactg caacctccacctcctgggtt aaagtgattc tcctgcctca gcctcccgag 90000 tagttgggat tacaggcatgcaccaccatg cccagctcat tttcctattt ttagtggcca 90060 cagggtttca ccatgttggccaggctggtc ttgaactcct gacctcaagt gttccaccca 90120 acttggcctc ccaaagtgctaggattacag gcgtgagcca ccgtgctcag ccatttgcgt 90180 gatttttaaa gatgtgcagaataatgccat taaaaaaaat acacatacat gtatatatat 90240 acacgtttgg ctgggtgtggtggctcacac ctgtaatccc agcactttgg gaggctgagg 90300 caggaggatc acttgagcccaggtgtacaa gactagcctg ggcgagatag caagacccca 90360 tctcaacaac agaaaggataattaggtatg gtggcatgag aggatcactt gagcccagga 90420 gttcgagtgt tatcaggccactgcactcta gcctggacaa caaagcaaga ccgtgtctca 90480 aaaaaataaa aataaaaagtatttgtatgt ggtcatagtc aaaaaacgta catggaagga 90540 aaatgtcttt atttatttatttattttttt ttttttaaga cagagtcttg ctctgtcacc 90600 caggctgggg tacagtggtgtaatctcagc tcaccgcaat ctcggcctcc cgggttcaag 90660 cgattcttct gcctcagccttctaagtagc tgggactaca ggtacccgcc accacaccct 90720 gctaattctt gtgttttcagtagagacagg gtttcaccat gttggcaagg ctggtctcga 90780 actcctgacc ttaagtgagccacccgcctt ggcctcccaa agtcctggga ttacaggtgt 90840 gagccactgc gcttggccaggaaatatcta atttagtaag tatttatatc tgggaaagga 90900 agggtcaggt ggtgattcataggaactcta aagtctatgt ataatactta gggggacaga 90960 aggaaataaa gcaaaatgctgatatttgat tgttgagttg tgtatatgtt agaagtataa 91020 cataggagat ctgattgatagtaggagaat gtttttaggt ggtaaaagtg gaaccgtggt 91080 ggtttgtttt ggcagtagaatcagttggtc atagtttgta tgtggaaggt aataaacaga 91140 ccatgttaag gatgacttccggaattttgg tctgagtagt gggtggatga cagtgtcatt 91200 catgagggaa gatgaagactgaggtaggaa caggtttggg agaagatgac atgttccctt 91260 ttagacaagt ggaattatggaagatggcag gtaggtggtt agctatatga atttgagata 91320 aaagatttag gatggagatataaatttagg agtaacagcg tatctatggt attgtaagcc 91380 ttaagaatgg gtaggatcagccaggaaata cagatgtata tgcagaagag aggagtcaag 91440 gaagccaaga caagttaatgtttaaagtga gtgatgtagt ccatgggcag atgctgctga 91500 gagggctgca aacaccagtgaccctacaac atttttaaat gtcgtcttcc tgacagcagt 91560 gatcagtacc tgcaacgatcttatttattt ttttcatgtt agtctccaca cacttgaatg 91620 tagacttttt gaaggcaaaatcattgcctt ttctgagctg ggagcatgtc tggcacatac 91680 caagcactca acagttgatgtattgacttc atccagatac tctgagggcg agttatttcc 91740 tgctactagc ctttcacctttcaatgttta agagcacaaa tacagagatg ggcacgtttt 91800 ggcatttctt attttgataaccttttcctg gtaagatttt ttaatgttga aaaaaaaaaa 91860 caagaaaaga gggttaaaaatagtcttatg tcagatcctg tgatagaatt cacacttggc 91920 ttaagctgct gggcaccttcctatcttgga tgtcatatta gcttatctac agcagaattt 91980 ttactgtttt atgtagtaaggaagcaatta tatgattatt ttacagacaa attattcttt 92040 atcttttatt tttttagacggagtctctct ttgtctccca ggctggagta cagtgtcgcg 92100 atctcggctc actgcaacctccgcctcctg ggttcaagca attctctgcc tcagcctccc 92160 aagtagctgg gcttacaggtgtccgccacc acacccagct cattgttttg tatttttagt 92220 agagatgggg tttcaccatgttggccaggc tggtcttgag ctactgacct caggtgatcc 92280 acccgccttg gcatcccaaagtgctggaat tacaggcgtg agccaccgtg cctggcccag 92340 acaaattatt atactctgagtgttagaggc ttaggatgtt ttcacttgat gctatgggag 92400 gaataagtaa taagatatgatacacaacca aagacctttc ttcactatgc ttctagtagc 92460 tagtactatg gatgacacatggtaataata ttggttagca tttgtcctca atttactgtg 92520 ctagttactc ttctaagccccttacaggta tatatttttt ttcatcaata atcctctaag 92580 gtagttttta ttattgacctaattttataa atcaagaaaa ttaagaccca gagaagtaag 92640 taacttgtcc aagatcacatggcttataag tggtagagcc agaatttgac cccagatgtt 92700 gtgactacat tgtctctccataagcaggtt caactctttt gactggatgc tgttccaagg 92760 tcacttcctt agagaagcctttgctgacaa ctaccctcct gtgccctcct ccaaggctgt 92820 ccattgttct agaactttgaatactcatct tagaataaag ctggtctaat ttttacagtg 92880 ttatagaatg gatctctgactgcaaaagtt ggtcataatt atctttttat gttctagtga 92940 aaggcaaaga acaagagaagacctcagatg tgaagtccat taaaggtaag ttctgccctt 93000 ggcagtccac tgcattaaaaagtgatgtgc tttgcatttg tgagttcttt aatcctgtta 93060 tactctctct tttggcattaatcatttctg ccttatttta taattactta tgattttgat 93120 ttatttccct ctttaacctgtataatgctt taacatctag catataataa gtaggctttt 93180 tttttttttt tttttttggagacggagtct tgctctgtta cccaggctgg agtgcagtgg 93240 cgcgatcttg gctcactgcaagctctgtct cccgggttca caccattctc ctgcctcagc 93300 ctccccagca gctgggactacaggtgcacg gcgccacgcc tggctaattt tttgtatttt 93360 ttagtagaga cagagtttcaccatgttagc cagtatggtc tcgatctcct gaccttgtga 93420 tccgcccgcc tcggcctcccaaagtgctgg gattacaagc gtgagccacc gcacccggcc 93480 gtaagtaggc tttttttaccttaattttat ttttttgaga tggagtcttg ctcttatccc 93540 caggctggag tgcagtggtgccatctcggc tcactgcagc atccacctcc cgggttcaag 93600 cgattctcct gcctcagcctcccgagtagc tgggattaca ggtggccgcc accatgccca 93660 gctaattttt gtatttttagtagagacagg gtttcaccgt gttggccagg ccagtctcaa 93720 actcctgacc tcaagtgatccactcgcctt ggcctcccaa agtcctggga ttacaggcgt 93780 gagccaccat gcctggccataagtaggctt ttactgagcc ttgtgtgtat tggctatcct 93840 agtgattaca gtgaaccagtgcccttctta ttaatcacac atttaattgt tccctaaaag 93900 tgattagttc actttatttatttagtaaga caaaaaatga agaatactct taactgagca 93960 gtctgttaac tgtaggaaagcactgacact tataaggctt agttttctgt catttatcca 94020 gaagtatggt tgattacagtttttactttt ttatttgaat gaacaacctt aatttaaaat 94080 atattttgtt tattttttgttgggatcgat acattgtcct tgtttataga ttagagcatg 94140 ctttttaaag atgctgtattactcactgat tttatttgtc cagtgtacag agattgaagt 94200 gggaaaatta taatggaaattgtttccata gtcattacat attaatttca tcaatttatt 94260 tccataaaat ctgtagattgctacttattt agatttttcc ttcaaatgtt tttatgttgt 94320 attgcttgca ctgagtatttattctatatg ctcaatttgc tggagaagaa gactaattat 94380 aacttaggca agttgtaaaattagggaaaa aagtaaggta ccttacagcc tagtttactt 94440 atttcttatg taaagccagttagattccac attagttcaa actgccttct ttgagcaaaa 94500 cttgattggc agtgataaaggcttaaagcc cttctcaagc agagacctgt aaagactaga 94560 tctgactgta gtagaaggaaggaacttaga tgtttcaggc agtgagaaca ccagtcttcc 94620 actctaaact ttgccactaacagtatgacc ttgggaagtt gtaactttct tcagattctt 94680 catttgttga atggggggattggcctagct aatttctaaa tctctactgg gctaaaaaat 94740 tctgtgctta tactctgattatgaagtaca taatctgtgc ttaacattca ctgacttatc 94800 cttaggataa tacagaagcagtacaagaaa cagcccctca agatgtttgc agtctggtta 94860 gaaagacaaa cttatacacagaacagtagc aaatagacca aaataataat agctgccatt 94920 tatagaacac ttcttctgttctgggcatta gacaaaaact gactataacg gtgaacaaaa 94980 aagacttagg tcctgccctcattgaactta cagattagta ggggagagga acattaatca 95040 agtaattcca cagatggcttagcctagatt ggtagtgatg gaagtaaaga gatgtgaacg 95100 gacttgaaaa aaaattcggaggcaaaatgg atagaagttt attattgatt aaatatgagg 95160 tgtgagagag agggatatttaagattgata cctaccttct ggcttgccta acagaaccaa 95220 aacaggaaat tatatgttcagttttgttat gttgggtggg aggtgctttt gagtcattca 95280 tttatatatg ttatatatgttattttatat gcatagtaat tttaaggtct gagttttaaa 95340 ccaaaggtta gagagtgattttttagagtc tagcaaacct aagttgaaat cctgcctgtt 95400 gaaatggctg tttactagctcattaaccta gggcaaagta ttcaacttgt tttcattttt 95460 gtcttcatct ctaaaatgaggaaaatatgg tcttacaaga ttgtcctgag agatagatga 95520 aataatatcc aaaaaaaaaaaaggtacata gagaaactcg tatagtgcct ggtatatagt 95580 aggtcctcca ttggtagctatcattatcta gttttaacat agccttcagt ttgttgaatt 95640 agtcaaactg agtgaagcactgcaaggaat tcagaggaat ttgagatcaa caaatgattt 95700 ctgaagttta gggaagacttcatggcaatg acacttacct tgtataaaag ttgaagaata 95760 agaaagattt gaatgagagattctttctct tctccctacc agcccagctt cttatttgag 95820 gatatattgg gcaaaggggccttcagacaa gtagagggag atttttacag aaagattgag 95880 atgaaggtat agaaggctgtaaagaccaga aaagagaatt gagacagagg aagcaggaag 95940 ccactgtagg tttttgagcaagatattgat gctgtaagta tggtgtttat gaaaggttag 96000 tctggaagag atttgcaggatggagacccc ggaagttttt ttgttataat acagaaagac 96060 ttgcactgag ggtgaggtgttaaaaataaa caggtaagta aatgtttaaa catcttgaag 96120 gaaaagtcaa caaatcttggcaagtaaaca gataacagtg aaaaagaatg ggaccaagat 96180 tttgagtttt ggagactggtggattgaaca gacagggaaa ttgagaggag aatcagatga 96240 tgatgtttta agttgatatttagacagatt gtgcttgaga tggtaaagtc aatgtgggtg 96300 ggaatgctta gtagcgagtaatcagtgata caagaccaaa gcccaggtca aagacaagtc 96360 acagatacag atcagggctttttcatctgc tccacagagg tgtaccctag gagctgttgc 96420 aaacagtcca tgtggagggtgtgagtaaga tgtttccctt gaatttgcca gaattacttt 96480 tttgttgttg ttgttgttttttctgagaca gattctcgct ctgttgccca ggctggaggg 96540 cagtggcgag atcgcgcagctcactgcaac ctctgcctct cgggttcgag tgattctcct 96600 gcctcagcct cccaagtagctgggattaca ggcttgtgcc accaagccca gctaatttct 96660 tttgtatttt tagtagagatggggtttcac catgttggcc agactggtct cgaactcctg 96720 gcctcgtgat ctgcctgcctcagcctccaa aagttctggg attacaggcg tgaaccactg 96780 cacccggtcc cttgttaagtttattttggt gggaagcaaa ggaggtttca gcttttaaaa 96840 agtttgaaaa ttattgctctggtaataatt aaagatttga gagtaaatat gctttctagc 96900 agaaagaata aaagaagaacagatagcctc aagaagggga gccaaagaag caggctatat 96960 ctgacacact gggtgttgataaatgggtat taaaagaatg agagcaatga gcagatagaa 97020 gaggaaatta ggagagtataataccatgga gaccaagaaa gatagactat caggaaggag 97080 tggtaaaaat aagttactagttctaagaga gatgttaaga gggaccgggg aaagccttgt 97140 acaaatgagt tagtagcattttacattata tacatctaat taagaaacaa tgcgagagtc 97200 tcaccattcc tatagactcttacttgtact tgtctgaaca cgaaaactgg cttttgttta 97260 taaataagct aaaaattattttgctccaat ttctcatgaa aataaaaata aaccttcttt 97320 taacattgaa aaaatagtttgaagacagtc actcttcatt ttgtaattcc cacaactatt 97380 attgaatgac tgaaattatctttattctga agccaaaggg gtgatactga tatttcttca 97440 gactactaaa aatatattttatgaattttt agtgtgcttt atcttttttt gttttttttt 97500 ttgagatgga gtttcactcccgttgctcag gctggagggc agtggtgcaa tctcagctca 97560 ctgcaacctt cgcctcccagattcaagcaa ttctcctgcc tcggtctccc aagtagctgg 97620 gattacaggc acctgcccccacacccagct aattttttgt atttttagta gagacagggt 97680 ttcaccatgt tggtcaggctggtcttgaac tcctgacctc aggtgatcca cccaccttgg 97740 cctcccaaag tactgcgattgcaggcatga gccaccatgc ctggcctgag gaatattttt 97800 ctaggttccc cccaccccaagcatttattc tgcaatttta gttttgttcc taaagcaagc 97860 aaggtttaag gatttaaaaataatccgtat tttagaatgc tttctggctt tgttactttt 97920 tatccacagt agaagttctcagagaatgat ctccctcttt taatttaact ttttggcaca 97980 gtattttgag aattataaataatattagaa tgttttctgg ctgggtgtgg tggctcatgc 98040 ctgtaatcct ggctacttgggaggctgagg caggagaatc acttgaacat gggaggcaga 98100 ggttgcagtg agccgaggtcatgccactgc actccagcct gggtgacaga gcaagactct 98160 gtctgggaaa aaaaaaaaaaaaaaaaagag tgttttcttt cctattttcc accacttgat 98220 taagttactt ttcctcttaagtattttttg ctgagtatgc tgacttaaga gtaatgttac 98280 aaaatttaat ttttaaagttctctgaaagc ccctttatga gagttttagg ctatcaaatt 98340 gtgtttaatt cttaacaattttttgaaaaa ttatagcttc aatatccgta cattccccac 98400 aaaaaagcac taaaaatcatgccttgctgg aggctgcagg accaagtcat gttgcaatca 98460 atgccatttc tgccaacatggactcctttt caagtagcag gacagccaca cttaagaagc 98520 agccaagcca catggaggccgctcattttg gtgacctggg taagtaacta tcatttttta 98580 ttaacttgta ttagaaggatttgagtacaa tatgtgaaac ttctgtcata ggatacagaa 98640 ctatataatt ggaaagtgctttggaaaaaa tgtatttaaa ataacagcta caagtataat 98700 gggtagctgt gttgtgttcctgtaaatata gaatataaag catgcccagt agaaaaacaa 98760 gcatttccag aagaaatatatctgatcact aaatataaat atatgaaaaa gatgtctcac 98820 tttattactg agggaagtgcaaattaaaat aatcagttaa tgttctccta acacattagc 98880 atatttttta aagtttgacaatttgaatgt cagtgaagat gcagggaaat acccctccta 98940 tttagtgata atataatctggtgaagactc tttggaaagc aatttggaaa tcagtataaa 99000 atatgcatgt catttaggccactctttcta agacctagcc ctcagatatg ctcattcata 99060 tgtgcaggtg tgtatgtgtgtgtgtgtgtg tgtgtgtgtg tgtatatgta tgtatgtatg 99120 tatgtatgta tgtatgttgaaggctattca ttatagtatt gtttgtgata gcaaaaaatt 99180 atggacaaca tataaatatctgttataggg aaataaccaa attgtggtat acgcatgctc 99240 tggagtataa tatagccatttgtttctatt tatttatttt cttgagacag ggttttactc 99300 tgttgcccag gctggagtgcagtggtatga tcatggttca ctgcagcctt cacctcctgg 99360 gcacaagcca ttctctcgcctcagcctcca gagttactag gactgcaggc atgtgtcacc 99420 acacccagat aattttttaattttttgtag agacagggtc tcactatgtt gcctaagctg 99480 gtctcaaact cctggcctcaagcaattctc ccacacaggc ctcccaaagt gctgggatta 99540 ccaacgtgaa ccaccacacctggttcagtg tagccattta gaaatctaaa aaagacgtgg 99600 gaaaatgtct aaggcatgtttaaatgtgag aaaagcaagt cacagtatgc atggtaaaat 99660 ccgttatatt aaaataagttcttccaaaac aaaaacatat gcaggagacc tttattttgt 99720 cagtatttct tacccaaatttctgcactta gaaaattgca tgtcatgttg tcataagttg 99780 aaaaaaagat ccatgaaccaatggacttct aataaaatca gtcctgcttt tgacatctct 99840 ctctactttt gtgtatattcaaaccagagt gtcaatgtgt ttgtggggca cacttagcaa 99900 taatacatag cagacaaaatgcatatagct cagagagtaa aattgtaagt tttgctagat 99960 cactcataaa ttgctgatgagaatttaaaa tggtgcagat gctctggaaa acaggcagtt 100020 tctttctttc tttttttttttctttttgag acagggtctc actctgttgc gcaggctgga 100080 gtacagtggc gtgattacaactcactgcag cctcaccctc ctcaggttca ggtgatcctc 100140 cctcagtctc ctgagtagctgggactatag gcatgcacca ccacgcctgg ctaatttttg 100200 tatttttttt ttttttttttgtagagacgg ggtttcgcca tgtttcccag gctggtctca 100260 aactcctgga atcaagcgatccacttgcgt aggcctccca aagtgctggg attacgggcg 100320 tgagctactg tgcctggcctaggcagtttg tttgtttgtt tgtttgtttg tttatttatt 100380 tgtagacgga gtctcacaggctggagtgca gtggcccaat ttttggctca ctgcaacctc 100440 cgcctcccag gttcaagctattctcctgcc tcagcctcct gagtagctgg gatgacaggt 100500 gcctgccata atgcctggctgatttttgta tatttagtag atatggggtt tcaccatgtt 100560 ggtcaggctg gttttgaactcctgacctca ggtgatcagc ccgcctcggc ctcccaaagt 100620 gctgggatta caggcatgagccgtcatccc tggctggtgg tttcttatga cgtgaaacat 100680 gcaattacca tatgacctagcagttgcact ctgtatttat cccagataaa tgaaaactta 100740 ccttccaata aaaacctgtgcacaaatgtt catagcagct taatattgaa aaactggatg 100800 ttcttcagca ggtgaatgaactggttcatt cataccatgg aataccattc agcaataaaa 100860 aggaacaaac tgttgatacatttaaccacc tggatgaata tcaagggaat tatgctgtca 100920 gacaaaaacc agtccctaaagactacatat agtatgattc cgtttggata atattcttga 100980 aatagagaaa ttaagagaaatgaaaagatt agtgtttgcc agatgttaga gacagggagg 101040 tgagaggggt aagtgggtgtagttataaaa gtgcaacatg agggatcttt gtgatgttga 101100 agttgtatct tggcagtggatgcagaaatc tcaatgtgat aaaattacaa agaactaaaa 101160 acaagaatga gtatagataaaactggggaa atctgaacaa gttagagtgt tgtatcactg 101220 tcagtatctt agagtgatattgtactatag ctttgcaaga tgttaccatg ggagaaacta 101280 aagtgtacaa gggatctctaggtattatta tttttttaga gatggggttt cactatgttc 101340 cccaggccgg tcttgaactcctgggctcta gtgatccgcc tgccccagcc tcctaaagta 101400 ctggaattac aggcgtgagcgaccatgcct ggccctttca gtattgtatc ttagaacttc 101460 atgtgaatct agcattatctcatagaattt aattaaaaga aattgtaaac ctcacagaag 101520 atcagaattt cctcaagtttgtgatgttga caaagatgaa ctagttgaca ctgacagtaa 101580 gactgaggat gaagacacgacgtgcttcaa aaaaatgatt tgaatatcaa tggattaaga 101640 agaactcttt tgacaaattgatgaaaccct cagtcagttt tataagaatg cccatcttta 101700 tgatcatgct atgaaagccaatttttaaaa aaattttttg tctttcctaa caattagctt 101760 gtggttataa tttaaatttagttaaatata agataaatga ttttttatta agtttagttt 101820 catttttcaa ggtacgatctcaaagctact ctttaaccta ctatgaatga ataatgctga 101880 gttcataaca tctttgtagatatatccaca attttccctc aggataagtg cctacaagtg 101940 gaattactgg actgaaaataatgcagtttg ctaagacttt gctatctgtt cctgaatgct 102000 cctccaaaaa ggttttgccagtttacatcc tcatgaccag cgaatgagag tgttgcctat 102060 tttcctgtgc ccttgttactgcttaataat ttttgaaaaa aatctaattt gacagacaaa 102120 aatgcatttt atgttaatttgcttttctgg gatttttaat gaggttgagt atagttttta 102180 atatttttat tggcccctttggaactagta tcataagttt tttttcttaa gaatttatgt 102240 agtctgggct gggcgcagtggctcacgcct gcaatcccag cactttggga ggccgaggtg 102300 ggtggattgc cgaaggtcaggagtttgaga ccatcctgac caacatggtg aaaccgaatc 102360 tctactaaaa gtacaaaaactagctcagcg tggtggcggg tgcctgtaat cccagctact 102420 taggaggctg agtcaagagaatcgcttgaa cccgggaggt ggaggttggt tgcattgagc 102480 cgagatcgcg ccattgctctccagcctagg caacaagagt gaaaagtctc aaaaaaaaaa 102540 aaaaaaaaaa aaaaaagaatttacatggtc tgaattgcca ttaaaagaga tatgagaatt 102600 attgagtaac aaataactttttaataattt aggcaagttt tggacgattg tactttgttt 102660 agaaaccaaa agcatagtatttgtagtttt tttatttact ttagttgcta ggaagtaaac 102720 tttattcaag gtctctggtaccagttgttg ctaaaagtga ttgactaatc tgtcaatctg 102780 aaattatttg ttgctgaactgctaattctt ttgcttctat cttttaggca gatcttgtct 102840 ggactaccag actcaagagaccaaatcaag cctttctaag acccttgaac aagtcttgca 102900 cgacactatt gtcctcccttacttcattca attcatggaa cttcggcgaa tggagcattt 102960 ggtgaaattt tggttagaggctgaaagttt tcattcaaca acttggtcgc gaataagagc 103020 acacagtcta aacacagtgaagcagagctc actggctgag cctgtctctc catctaaaaa 103080 gcatgaaact acagcgtcttttttaactga ttctcttgat aagagattgg aggattctgg 103140 ctcagcacag ttgtttatgactcattcaga aggaattgac ctgaataata gaactaacag 103200 cactcagaat cacttgctgctttcccagga atgtgacagt gcccattctc tccgtcttga 103260 aatggccaga gcaggaactcaccaagtttc catggaaacc caagaatctt cctctacact 103320 tacagtagcc agtagaaatagtcccgcttc tccactaaaa gaattgtcag gaaaactaat 103380 gaaaagtgag tatgtgattttcttgtgtgt acatatgtgt ctcactttct ttttttaatt 103440 tactaagcag aacttcagatgaggaataaa atgattggaa tatttttttt ctcctctaac 103500 tacttgtaaa tttgggagaatttggagagt gtagtagagt cagatcagtg tatggaaaag 103560 gagcaggagt gactggaccttctaagaagt gtgttatcag aattagtaaa tgaagggtca 103620 aatgtcctac ttttcccctccactgatttt gacatcaaac cattatccac atagccttat 103680 ttcctccctc ggtcttaattttattaatat tttactgcac tttgcagata aaatttttaa 103740 aaaattttta aaaattgccaataagtgaca tttattaagt tcagtgctta gtgtatattt 103800 ggattttatt tattagtcacaagacctttg tgcaggtagt aggcatgatt atcttttttt 103860 ttttgagatg gagtcttgctctgtcgccca ggctggagtg caatggcgcg gtctcggctc 103920 actgcaacct ccgggttcatgccattctcc tgcctcagcc tcccaaatag ctgggactac 103980 aggcgcctgc caccacacccggctaatttt tttgtatttt tagtagagac ggggtttcac 104040 catgttcgcc aggatggtctcgatctcctg actttgtgat ccgcctgcct cggcctccca 104100 aagtgctggg attacaggcatgagccaccg cgcccggact gattatctta tttacacatg 104160 agaaaaccag ggcttagaaaggttaggtaa cttcctctag gttgtacagt aaatgtggac 104220 ctagaagcat tttgacaagagcacctgttt ttttttcttc tctattagtt tagaaattat 104280 atactcttaa ttatcacctgggattttgat tagacagcct tcatgttctt tttcatctta 104340 aatgttcttt gtgtcttaaagggctaagtg atttcttcag atcttttagt tcactcattc 104400 tcagtgaact aaaatgaggtctaatctgct actgaatcaa gttttcagca tgttatttcc 104460 ttcctccctc cctccctccttccttccctc aaccaggctc ccgaggagct gggattacag 104520 gcgcccgcca ccactcctggctaattttta tattttagta gagacggggt ttcaccatgt 104580 tggtcaggct gatcttgaactcctgacctc aagtgaccca cctgcctcgg cctcccaaag 104640 tgctgggatt acaggcatgaatcaccacac ctgacggcat gttattttca tcgcaaagtt 104700 actgtaagct gggagaagtggcacacactt gtactcccag ctactcagga agcttaaggt 104760 gagaagattg cttgagcccaggagttttga gaccaacctg ggcaacacag caagacccca 104820 gctcaaacaa agaaaaaaagttattgaatt ttttatttct atggatcatt ttttgtagtt 104880 tcttattcct ttcacccttcattcccactt ttgatcccat cttttattta tttagtttta 104940 ttaaatgtat atttgtctgataattctgct atctacagtt ttttgtggac ctgactcagc 105000 atttctttgt ttcttcggattcagactgtt ggtggcttgt gattttagtg atttttggcc 105060 gtgaacatgt ttcttggacttttgtctgtg ggaattctct gtgtactctg tataaattaa 105120 gttacttcag gtgttttgcattttcttttg ccatgcacct ggggcctggg tcactaccct 105180 tctggtacca cttaaaactgaatttttgtc ttgggtgctc gtactgatcc tgtatgagta 105240 caggtttata cttactgtagaaatatggtg tttgattatg gggtattgtc ccagatggtg 105300 ctggagtatt aatatgctctctgttaaact taatgtgttg tccctgtaaa actccaaaat 105360 tctgaattcc agaatactactggccccaaa tgtttaagat aagggcactg cctgtatttg 105420 tttctgcctc ccactattttccttagttta acacaaactc acctttttaa aaaacatttt 105480 gagagaattc agtattgggaagagtttcta acctgtttct ggaaatggaa gtccaaagtc 105540 tgtttctgta attgttttttttttgagatg gagtctcact ctgtcaccca ggctggagtg 105600 caatgacgta ctctcagctcactgcaacct ccacctcccg ggttcaagcg attctcttgc 105660 ctcagccccc tgagtagctgggattacagg tgcccaccac catgcctggc tgatttttgt 105720 atttttagaa gagatggggtttcgccatgt tggccaggct ggtcttgaac tcctgacttt 105780 gtgatctgcc cacctcagcctcccaaagtg ctaggattat gtttctgtaa ttgtaataca 105840 tttattgttt ttagaaactgtctttgcttt agtggtaatt ttcaataaaa atagaaatag 105900 cagtggagtt attaaaagagcattagttac atttttccct ttttcattat cttcaaatat 105960 tatatatagt aagtttgacctttttaaaat gtatacttgt atcagtttta acacatacat 106020 agattcctgt aactgtcaccactataaggg taaagaacag ttagttcctt cacctttgaa 106080 gtcaagcccc acctctatcccaacacttgg caaccgctga tctttctccg tctcaatagc 106140 tttgcctttt ctctttttttttcttatttt tttttttgag acagcgtctt gctctgtcgc 106200 ccgagctgga gtgcagtgaggcaatctcgg ctcactgcaa cctccgcctc ctgggttcaa 106260 gcagttctcc tgccttagcctccctagtag ctgggattat aggcacgcac caccacaccc 106320 ggctgatttt tttgtatttttagtagaaat ggggtttcac catgttggcc aggctggtct 106380 caaactcttg acctcaagtgatccacctgc ctcggcctcc caaagtgctg ggattacagg 106440 cgtgagccac tgtgcccaatcaggactttt tttttttaaa tttacattca acttgtcatt 106500 tttttcttgt atggattgtgccttcagagt cacacctaag agccctttgc ctaagcaaag 106560 gtcatgaaga ttttctcatatgtttccttt taaaagtatt gtggttggcc aggtgccatg 106620 gcttatgcct gtaatctcagcactttgaga agctgaggtg ggcagattac gaggtcagga 106680 gatcgagacc atcctggctaatgcggtgaa accccatctc tactaaaaat acaaaaaaaa 106740 aaaaaaatta gccgggcgtggtggcgggca cctgtagtcc cagctacttg agaggttgag 106800 gcaggagaat agtgtgaacccgggaggtgg agcttgcagt gagccgagat cgcgccactg 106860 cactccagcc tgggcaacacagtgagactc catctcaaaa aaaaaaaaaa agtattatgg 106920 ttttacactt tacgtttagatatatatctt ttttgagtta atgtcgtata agtatgaggg 106980 ttacgtcaga ttttttgttttttgtttatt tttacatatg gatgtctagt tgttctaata 107040 ccatttgttg aaaagacaacctttactcca ttgaattgcc tttgtacttt tgccatattt 107100 gtctaggcct gtttttggactcctttttct gtttcatgat gtgtgtgtct attcctttgt 107160 taataccaca tggtcttaattactgtatag taagtcttaa aattgggtaa tgctggcctt 107220 ataaaacgaa ttgggaagtttttattttta ctcttatttc cattttctag aagagattgt 107280 gtagaattgg tgtcatttcttctttagata tttggttgaa ttgggaagtg atgccatctg 107340 ggcctagggt tttgttttttgtgtgtgaga cagagtctca cttctgtcac ccaggttgga 107400 gtgcagtggt gagatcttggcttactgcaa cctctgcctc ccaggttcaa gttatcctcc 107460 tgcctcagcc tcccaaatagctgggattac aagcgtgtgc caccatgccc gactaatttt 107520 tgtattttta atgcagacagggtttcacca tgttagccaa gctggtctcg aacttgtgac 107580 ctcaagtgat tagcccaccttggcctccca aagtgttagg attatagatg tgagccaccg 107640 tgcctggcag gggcctagggttttcttttt cagagtattt taaactatga attcagatta 107700 tttaatagat ataggactatttaagttatc tgtttcttct tgagtgaatt tttactgtag 107760 tttatggcct ttgagtaattaattgtattg aattgtcaaa tttatgagcg tgtaattatt 107820 tatagcattt cgggtttgtagtggtatccc tcttttattc ctggtgttgg caattgtgtc 107880 ttgtttttct ttgtcagattgtatagggat ttattagtct tttcaaagaa ctagcttttg 107940 ttttgatttt tctgttgttttgttttcaat tttattgatt ttctgctctt tattatttct 108000 tttctattat ttctgcttgctttgggttta ttttactctt ttttttttct ccaagttgct 108060 taaagtagaa acttagatttctggtttgag acctttcttt tctaagataa gcatttaata 108120 ctgtaaattt ccttctaaccactgctttag ttacaccccc acaaattctg gtattttgaa 108180 ctgagcacaa atgaaatgttctaatttccc ttgaatctta ttcttttacc aatgaattat 108240 ttagaaatat gttatttagtttgcaagcaa ttggagactt ttttcctgtt atttttctac 108300 catttatttc tcatttcattatattatggt cagagaatat attttgaatg atttcattta 108360 ttaattttta aaaataacattaaaaaattt tttaaaatgt gaatatacca catacagtat 108420 aaagattgta cattctgtttttggacagtt ttctataaat gtcaagttga tttagttggt 108480 taatgatggt gttcagtttttctttattct tgctgatact ttgtatgcag ttatatcact 108540 ttattactca gaagagtgttgaactttcca actacaattt ttttttccaa ttttactttc 108600 agctctatct ggttttgcttcatgtatttt gaggctctgt tgttaggtgt gtacacattc 108660 aggatgatat cttctgggtgaattgcctgt tttatcatta tgtaattccc tctttatggt 108720 aattttcctt gttctaagatcagaaatatc tgttgtccaa tttatataga cactgcagct 108780 ttcatttgat tagtgcttgcatggcatatc tttttccatt tttttacttt tgatctacct 108840 ttataattct atttaaagggggcttcttgt aggcagcata tagttgggta gtgttattta 108900 tttatttatt tatttatttatttatttatt tattgagaca gagttttgct cttgttgccc 108960 aagctggagt gcagtggtgcaatcctggct taccacaacc tccacctcct gggttgcagt 109020 gattctcctg cctcagcctcccaagtagct gggattacag gcacgcgcac catgcctggc 109080 tgattttttg tatttttagtagaaacggat tttcaccatg ttagccaggc tcgtcttgaa 109140 ctcctgacct caggtgatccacctgctttg gcctcccaaa gtgctgggat tacaggcgtg 109200 agccactgca cccggctgagtcatgttatt tttaatcttt tctcacaata cagggttttt 109260 gttggtaaat ttaattattttaatataaat tttagtataa ttatttacat taaatgtaac 109320 tgttgcactg gggtatttataatgtgtaaa tataattatt ggtattaata taattatatt 109380 actcataata atattaatatctttggattt agattaccag tttagtatat gtttttctgt 109440 ttctccctct ttgatttccccttttttgct tttttttttt ttttaattct tatttttttt 109500 tagtatttgt tgatcattcttgggtgtttc ttggagaggg ggatttggca gggtcatagg 109560 acaatagttg agggaaggtcagcagataaa catgtgaaca aggtctctgg ttttcctaga 109620 cagaggaccc tgcggccttctgcagtgttt gtgtccctgg gtacttgaga ttagggagtg 109680 gtgatgactc ttaacgagcatgctgccttc aagcatctgt ttaacaaagc acatcttgca 109740 ccacccttaa tccatttaaccctgagtggt aatagcacat gtttcagaga gcagggggtt 109800 gggggtaagg ttatagattaacagcatccc aaggcagaag aatttttctt agtacagaac 109860 aaaatggagt ctcccatgtctacttctttc tacacagaca cagtaacaat ctgatctctc 109920 tttcttttcc ccacatttcccccttttcta ttcgacaaaa ctgccatcgt catcatggcc 109980 cgttctcaat gagctgttgggtacacctcc cagacggggt ggcagctggg cagaggggct 110040 cctcacttcc cagatggggcagccgggcag aggcgccccc cacctcccag acggggcagt 110100 ggccgggcgg aggcgccccccacctccctc ccggatgggg cggctggccg ggcgggggct 110160 gaccccccac ctccctcccggacggggcgg ctggccgggc gggggctgac cccccacctc 110220 cctcccagat ggggcggctggccgggcggg ggctgccccc cacctccctc ccggacgggg 110280 cggctgccgg gctgaggggctcctcacttc gcagaccggg cggctgccgg gcggaggggc 110340 tcctcacttc tcagacggggcggccgggca gagacgctcc tcacctccca gatggggtgg 110400 cggtcgggca gagacactcctcagttccca gacggggtcg cggccgggca gaggcgctcc 110460 tcccatccca gacggggcggcggggcagag gtggtcccca catctcagac gatgggctgc 110520 cgggcagaga cactcctcacttcctagacg ggatggcagc cgggaagagg tgctcctcac 110580 ttcccagacg gggcggccggtcagaggggc tcctcacatc ccagacgatg ggcggctagg 110640 cagagacgct cctcacttcccggacggggt ggcggccggg cagaggctgc aatctcggca 110700 ctttgggagg ccaaggcaggcggctgggaa gtggaggttg tagggagctg agatcacgcc 110760 actgcactcc agcctgggcaacattgagca ttgagtgagc gagactccgt ctgcaatcct 110820 ggcacctcgg gaggccgaggcaggcagatc actcgcggtc aggagctgga gaccagcccg 110880 gccaacacag cgaaaccccgtctccaccaa aaaatgcaaa aaccagtcag gtgtggcggc 110940 gtgcgcctgc aatcccaggcactctgcagg ctgaggcagg agaatcaggc agggaggttg 111000 cagtgagccg agatggcggcagtacagtcc agcctcggct ttcacaactt tggtggcatc 111060 agagggagac cggggagagggagagggaga cgagggagag cccctttttt gctttctttt 111120 ggattatttg aatttttccttaaatttatt tatcttactt atttatttat ttttttgagt 111180 gattctcctg ccacagctcccaagtagctg ggactgcagg catgtgccac tacacccagc 111240 taattttttt gtatttttagtagagacagg gtttcaccat attggccagg ctggtcttga 111300 actcttgacc tcaagtgatccacctgcctc ggcctcccaa agtgctggga ttacaggcgt 111360 gagccaccat gccctgcctttttctagaat ttatatattg agttcttgat tgtatctttt 111420 tatgtaggct ttttagtggcttctctagga attacaatat acatactttt cacagtgtac 111480 tcacatttaa tattttgtaacttcaagtgg aatgtagaaa acttaaccac cataaaaata 111540 gaactaggga tgaggttaaaaaagagagag aaaagaaatg taataaagat ttaataacac 111600 cgtttttttt tttttttctctttttttttt gagacagagt ctctctttct gttaccaggc 111660 tggagtgcag tggcgtgatcttggctcact gcaacctccg cctcctgggt tcaagtgttt 111720 ctcctgcctc agcctactgagtagctggga ttacaggtgc gcgccaccat gcccagctaa 111780 tttttgtatt tttagtagagacggtttcac tgtgttggcc aggatggtct cgatttcttg 111840 accttgtgat tcgctctcctcagcctccca aagtgctggg attacaggcg tgagccaccg 111900 cgcccggcta agtctttaaatatttttttg acattgcact ttttctcttt tccttctagg 111960 attttagtaa cccaaatgttagttttgtta ttgtttggca ggttcctgag gctttcctta 112020 cttctttaaa tttttttttcctgttgttca gcttcgaaaa tttctattca tctgtcttca 112080 aattcactgg ttctttcccgttatttccat tctgttattg agtctttgta gtgaatttta 112140 aattttgttt attatgttttttagttctaa aattttcttt ttttgtgtat gtcttatact 112200 ttgctcctga aactcttatttgtttcagga gtgatcttat ttcttagagc atggttttag 112260 tagctactta aaatttgttttatcatccca gcatatgtgt cctcttgatt gtcttttctc 112320 ttgtgagata atgggattttctggttcttt atatgacaat taattttgga ttgtatcttg 112380 gacagtttga cttacgttacatgattctga atcttgttta aatcctgtgg aaaatattga 112440 agtttttgct ttaacaagcagttgacctag ttaggttcag tccacaaatt ctaagcagca 112500 ttctgtcggc tctggttccatcatcagttc agttttgtat cttatctgct tatgtgcctt 112560 tctgtgtcca gtctgggacctggccaatgg tcaggtccca aagcctttgt acacttttag 112620 aagcagggcc atgcacacccagctcacgag tggccccggg agtgcacata caactcgacg 112680 ttttcatggg ctccttcttttctgtgatgt ccctgacacg ttctgccttc taagaacctc 112740 cctttatccc tttcctgttgtctggctaga aagtcagggc tttagattcc ctatacttca 112800 gcacacttcc tgtagctatgtcaacctctg tggccacgac ttcttcttct tgggactgca 112860 gtttctcttg tcagaaagtaggattcttgg agctgctgtc attgctgctg tggctgctct 112920 gatgctgcct gggagtcgaaggagagaaag gaacaaaaca aaacaaccca ggggatttcc 112980 tccactctct ttgatccgtgagagccccct ttcctgttcc tcagaccaga aatagagggc 113040 ctgtcttgga acttcttctttgtgcatctg gtgtgcagtt tcagcttttg agtccaggcc 113100 aggaggtgct ggacaaacttgtcaggagta cggaggtact gcaagttctg attacttttc 113160 tcagtccacc tgcttccaagtccttggatg catttgtcca ttgttttgag ttgcattcca 113220 tgggagagac agaagagtgtgcttatttca tcttgacata cttattagga tttcatatca 113280 aatcaacgga tgatattctctatattaatt tgctgttttc cctttagcaa gcacattagg 113340 aaaataacac tttaacacccgcctttggtg gtttctgtca taattattaa tacttgactt 113400 tttttttttt tttgagacggagtctcactc tgtcctttga ggcattgtcc ccataaactt 113460 ttggtaaagc atcaataattttatctttca tccacacaag cttcaccata aatttgatgt 113520 ttattcttcc attttagcagaattcatgtt gctccaatag gggctgtctt caaactgatg 113580 ttttctcctt cttagtgcctcagagtagat cctgttcaga tacgttataa caggttaata 113640 tgagtttatt ttggtgtaaaagtactttga aattcatgca tagttttttc atcatatgca 113700 ttttccatag ctttgaacacccccatgtaa ctctcctctt ccacaaacca aacaatgaaa 113760 aagcaccttt gtgatggaagtttattttgc aataggaact cacagtgatc taagccctgc 113820 tattcatgaa tataattcattactggagtc caagttgctt tttggttttt gaagttctct 113880 tcttcccttg caggtatagaacaagatgca gtgaatactt ttaccaaata tatatctcca 113940 gatgctgcta aaccaataccaattacagaa gcaatgagaa atgacatcat aggtaagcag 114000 tgcttgaaac tatggcaaaaaaaaaatgac aaaaaatgca cagaactgac aattttcgtt 114060 attgactaag ataattttttcttaacatgg aatttagcag ttcccttcct aatttgtttt 114120 ctgagtattt tttatatcggattatagctc actttaaaag tttctcggct gcattcggtg 114180 cgagggtctt tgcctgggccagatgggctg cagtgtagcg ggtgctcagg cctgcccgct 114240 gctgagcagc cgggccggcgggcggctacg ctaaccggca cagaccaccg gatggactgg 114300 ccggcagccc cgcaccagtgcacgaagtgg gcgggacaga aacttctggg gttggaagtc 114360 cagtgaggct aaaagccggtaccaaagtct ctaggcatca gggctgcagc ccaagagtct 114420 cacgaccagt gggcaactggatggccagac aggtgtctca gtggtggcct ctccgtctca 114480 gggcttcatc ccacttctcagtgggcctga cgtccctggg caccctggat gtctacctgc 114540 attagccaga gccatcacatggcctgtgac ttgccttttt ttgccagttg attgtgccac 114600 acacagtgtc atttctgtgtcatttggcac agctggaggt gcaaggagga gggcagcctc 114660 atgtccagtc ccagtttcacgtaactttat tcttctgaat aaagacaatt tgctaacctt 114720 aaaaaaaaaa aaaaaaaaaaagtttttctt atatgttgga cccaaattct taggctttaa 114780 cctgaataac aatgacagcaagatcaataa atagtacaca tttattaaac actcactgtg 114840 tcccagacaa tattccaagcactttttatg gatagactca ttttaacttc taaagaactt 114900 tgtgggataa atacagttattttatagatg aagaaactga agcacagaga agttaagtgc 114960 tttgtccagg gtaacagctcagatatggca gagtcaggat ttgaaactag accctcacat 115020 accttaactg ctgtgctgtggcagtgtttt tcatactgta ggttgggacc agccttctct 115080 tatgccctca ccccctgccaaaaaaaaaaa aaaaaaaaaa aaatatatat atatatatat 115140 atatatatat atatatatataatatatata tatataaaat atatatatat ataaaatata 115200 tgtattagta tatatgcatatatagtatat attatatatt agtatatata ctaatatata 115260 atatacatat tagtgtgtgtatatatatat atactagaat aaaaaaatca aagtatctca 115320 gagtagtaag gacaaacatttcagaaaaat gttttcatta tatatacatg tatgtatgtg 115380 tatgctgatt caacaaatatatttcttata ggttatagca aaatagtttg aaagctttta 115440 ctgtgtttta tcaggaagaccttaggtgaa cgtatattca cagataaaag aggttattta 115500 ttcattcaat aaatattacattctcataag tcctaatatt atgtattttt attcttcaaa 115560 aaagttagta tttgtgatttatgaaataag acatgttctt gcacttttag cagatctgtc 115620 ccgatgttgg gcttctttaatccttagtgt gggtgctttg cactcactca ctgctgggga 115680 cagcaagacc cctgttagtctcagctgtgt ttcttaaatt ggcccactgt accttccagt 115740 tagctattct ggggtccatgtcatgttggc tccattttcc ttttctttct cccacacaga 115800 tacctataac ggctataacataggcctggt ggctgttggt ggcttatccc tatctgcttg 115860 tatttaaggg gtactgtttcactgagtttt gctgacagat gttgtcatga gatttgaggt 115920 tttctgtgtt gttgctctatttttatgtgg gaatttgcta ctatcatcat ccctagacca 115980 gcttttccta gtaatacaacagggatgttc tgactgatta gagtttgcct gtttgaagaa 116040 ttggttggct agtgatttttttttgagggg agtctgtacc agttaatagc ctgactggcg 116100 tgtggataaa aaggaagcagtttcaagtca aataaaacac ttaaaatgaa accacactgc 116160 aactctcttt cttttacttaagcttaatca aattaatgat gatgtaatcc catgaaggaa 116220 aagtcttctg aaggatcaagttgataacat tttgtgatca aagaatttga gaaaacctct 116280 atcccagtgt ctatcattatatattttagg atgttaatta cctgtgtggc tttaggcaag 116340 tcatttttcc tccttgagccccattcttaa tcctgtccaa attatttgtc tcctcttgca 116400 gttggactat tttaatatagctgtccttca agtgagtttt gttcaaagga gccttcactt 116460 tagctcttac tgtgtacccactttgcatag tcttgtttta aatgtaatcc ttggattttt 116520 ggtgttgcta actaattactgtttttatgt gaggatttag agtgatccag aatctatact 116580 tgcactacct ccttcatcttccacaaatgt ttgaagtggt agaattttta aaaactttga 116640 aggtacagct gacagaatttgctgatggtt tggaagtgag tggtatgaga gggaaaaaaa 116700 ggaataaagc atgactgcattttttgtttg tttgtttgtt tgtttttgag acggagtctc 116760 actctcgcca ggctggagtgcagtggcgtg atcttggctc acggcaacct ccgcctcctg 116820 ggttcaagcg attcccctgcctcagcctcc caagtagctg ggactacagg cgctcgccac 116880 cacgcctggc taatttttttttttgtattt tagtagaaac ggggtttcac cgtgttggcc 116940 aggatggtct ccatctcctgacctcatgat ctactcacct tggcctccca aagtgctgag 117000 gttacaggca tatatataagcatataaagt gtgttatagc atacaaacag gtatatatat 117060 aaacatgcag tccacacagctgataggaat gaggcagtag tgaaggagaa gttgatgtag 117120 gagaggggac agttgttacaggaaagaagt ctggaggcag aagggatgaa ttccagtgct 117180 cacatagaag attgcttagatgggagcaag gacaatttat ctagagtcac aggaaagaat 117240 gcagtacacg ggtagagatgcaggtgagtt gaaagatgtg agagatgatg gaaataattt 117300 tctgattgct tctatattctcaaggaagca ggaagcaaag tcctcagcaa agagaataga 117360 agaggtgtta aatatttgagaaaggagatg tactgtagaa aaaaaaaaaa ctcagtttct 117420 ccttctgaac tctcacaaaacagaaccctt ccatgactct agttgtgtgg ggttttttcc 117480 ctgtcagcta ccaattctgcagatgattgt tcagtgaaca ccaactgggt gtcctctaag 117540 tcagttcagt tctcacactgtttacctgga gatagcatca gatcccacag attgaggact 117600 ctgtcccaca agactgcctccacttcagat gccagtctca agtacaagtt gtggcctgtg 117660 cttctgactg accttctataaattggagtt cccacagtcc cctccttggg ttcaataaat 117720 ttgctagagc agctctcagaactcagggaa atgctttaca tatatttacc catttattat 117780 aaaggatatt acaaaggatacagattgaac aggcagatgg aagagatgca tgggcaaggt 117840 atgggagagg ggcacagagcttccatgcac tctccaggtc atgccaccct ccaagaacct 117900 ctacagattt agctattcagaagcccccct ccccattctg tccttttggg ttttttgtgg 117960 agacttcatt atataggcatgattgatcat tggctattgg tgatcagctc aaccttcagc 118020 cccctcatcc cgggaggttggtgggtaggg ctgaaagtcc caaacgtgta attctgcctt 118080 ggtctttctg gtgattagccctcatcctaa agctctttag aggccacagc cacaagtcat 118140 ctcattagcc ttcaaaagaatccagagatt ccatgaattt taggcgctgt atgctaagaa 118200 actggctaaa ggccagttgcaatgtctcag gcctgtaatc ccagcacttt gggaggctga 118260 ggcaggagga tcgtttcaggccatgagatc aaaaccagcc tggtcaacat agtgagaccc 118320 ccttacaaaa aatttaaaaattggccaggc gtaatagctc ttgtctgtag tctcagctac 118380 tcagaaggct gaggatcactgagccctgga gttgaaggca gcagtgagcc atgatcgtgc 118440 cactgactcc ggcttgggtgacaaagtgag accttgtctc agaagaaaaa ggaaaaaaaa 118500 aaaactgggc aaagactaaataacatattt cacagtatca cagatttgta ttgtctagga 118560 aagtgaatgt aaacagaccaggacactagt atgatccctt ggtttcatga aggtcccact 118620 aaagtcatga acacaaagtgagactaggca tcatgttata tggtttttcc agccatgttt 118680 aacagctagc taaatagctaattgtttcgc tgcagtttat tttagcagtt ccttatttta 118740 gcacatttca tgttttaaaatttctaccaa taacatttta ataaactttt ttacagataa 118800 cttcacaaat ccataattttttaagttaca atcccagaaa tagaattgct cattgaaagg 118860 gtatgttcat ttttaaagttatgctagaaa ctgccaaatt gccttcagaa aaaggtgttt 118920 gtatccccac taacactagtgttagttttc ttgtgccctt gctcaagtat acatattatt 118980 aaaaacaatg ttgggccagtttactagata aaaggtgtag tgcctcctta ttctaatcta 119040 tttgattact agtgagtatgtatgtctttt cacgttggtc attttatgtt tgttcctttg 119100 tggattgtca tgtcctttgctcatttttct tttggaacat ttcttagtag tttataagag 119160 ctcttggtat tttaatgatagtaacctttt aactgtcatg catgctgcaa atcttttttc 119220 tgtttgtttg cctttgtattttgtttttgg agggtttcta tgtataggaa ttaaatttta 119280 tgttgttaaa tcttttgatttctgcttttg catatgtact tcaaaagact ttctatttta 119340 agatcaagtg ttacctgtattttcttttag ttctatttaa aacctcttaa tttatatgcc 119400 tgtgctgtta actcccaagttgattcacaa gtgtgtatac atagtttgaa tttagtggca 119460 atttaattat ttacaacttcttttgcagca aggatttgtg gagaagatgg acaggtggat 119520 cccaactgtt tcgttttggcacagtccata gtctttagtg caatggagca agagtaagtt 119580 agttcatatt ttcacattgtgcatcctagg gaatttgggt tcattgttag gaatgggctt 119640 cactcagcta aaaacaaagtatttttgaga atttaaatat tttggatatt tacaagatca 119700 tataaagcat actctatcttggttaacagt ttcttttaaa tataaattat gtgaactctt 119760 aaaattttca ttttcattttcaatgttaat atttcctaag ttaaaataat ttgtttttag 119820 ttctgaaata atttggggagtgattgagtc tgtagtgatt atgactatta gaattggttt 119880 atttatttaa ataatgcatgtcttcagatg gctctcctaa tttgttagtt aggctttaag 119940 ctaaatggat gctatataactaaatccaca tagatttgtt gaaatggctc cagaggtttt 120000 ttagatttat tactgctatgtgcccttaaa aaaaatctat tcattctttc acttaacatt 120060 tatcagaaga gtgctctgtgtaagacgtgg ttaggcatag tgccagtctt gaaggaagtt 120120 acagcctaat aaaagacatagggcatgttg tttggttact gtaatatgaa gtggcatgtg 120180 ttaaatgtca ggggagaactacaaagtcat aaaaaggtgg gagagattac atacaggtaa 120240 aggaatcagg aatgacaccatggggagtaa ggtagtgttg acctaggcct ttaagataca 120300 atagggacag tatggaaagagtatattttt cccacttaaa ctctttcctt ggtcgttccc 120360 tcaaattttc ccttttgtccatgtgcaggc actttagtga gtttctgcga agtcaccatt 120420 tctgtaaata ccagattgaagtgctgacca gtggaactgt ttacctggct gacattctct 120480 tctgtgagtc agccctcttttatttctctg aggtaaagtc tgcatttctt ttcacactct 120540 attcgagcat tccagcctctaactatcaat gctggggccc tgtctatagg aaataacaca 120600 gaagagccaa gtcatttccaaaaagatgta tcattgtttc aagttgtttc tgatggcaag 120660 agtaatttaa taatatattagagagaacat gaaaattcaa tgtattaaat aactctaatt 120720 ttgagaaacc taattaaactactgcatgta agagagtgca tgtttttaat tatttggagc 120780 tattttaaaa ccacagaatttgaaacttgc ttccagtgca taaattgcag accagacttc 120840 agaagagaaa aaaagtagtaaattttttct tatgctcatc atttttactt tagtcacttg 120900 ataggattgc ccagtgaagaagcatttgca acagacaatg agtatattaa tctttttgag 120960 gcatacagtt tagtataatgctctttgtta ggcttcaaca agtgaaatta ttttgttgga 121020 aagcaaatga ctattaagtagaaagaggat tcccagtctc acaaagcagt aatttagaca 121080 ctcgattctg cctctttacaagaatacagg tactcagttg atttgttttc tcactccctt 121140 tctttgctat aagtttaaatcaacaatttg tttaggttaa tatgtcctca tggaatggtg 121200 gaaatgatca gatataaaatatttggtttg gttagtttac tctttatatg tttgctggca 121260 aggaaccaca aatccagtttagtataattt ttactctagt tcactaaaag tttgcatcca 121320 gctgtgtagg tagtgtttgtttcttgttaa cttttttttc gtctaaaaga atactttaaa 121380 acttttcaat ctcaaatgactgtaacttgc tgacaggtgt taacagaaga agtagatctt 121440 tttgtttttt gcttatgacctgtattttaa tatttgagct tatagattag agattgtgag 121500 agaaatctgt ttatagtcttattttccctt gtgtattttt tcttcctagt acatggaaaa 121560 agaggatgca gtgaatatcttacaattctg gttggcagca gataacttcc agtctcagct 121620 tgctgccaaa aagggccaatatgatggaca ggaggcacag aatgatgcca tgattttata 121680 tgacaagtga gttatattgatagatggatt cagcagatac ttattgaaca tttgatatgt 121740 tttgtggaaa taaagatgaataaactcagt ctctgttgtc aaggagctca caggaggcag 121800 cataaaagct gcttttatatggtgtttgta aagctttggg ggttcttaga acaaaagttt 121860 ctgctgggaa aggggaggtgtatgtggggt aaacaggatg gcaatggtgg tgttcaagga 121920 gtgtttccca gaagagagattttgtttgga tcccaaagaa agaagggaat tttgctaccc 121980 agagaaggca gaaaacaacattctaggcaa aggcattggc ccagaagcca tggaaacgta 122040 ggggaaagtg gcactttcaagaaacttgag tttagataat caaaggagtg gggaataaat 122100 atgaggatgc tggtactaattggaatagat tgtaagggac cttgaatgcc tatttatggg 122160 tatattatac tttctgtataaatctgctca ggcacgttgt taattagttt tttattagtt 122220 ttcactgaaa atgagaggatggaaacatca tacagtaaac aaaattgaaa atatctggtc 122280 aggcagatga tgagcttgtggccagctctg taacgtatgg tattcttttc atttaacttt 122340 tcttactctg taaaaaaagtaattcgtggt cgggcacggt ggctcactcc tgtaatcaca 122400 acactttgag aggcagaggcaggtgaatcg cttgagccca ggaatttgag accagcctgg 122460 gcaacatggc aaaacccgcctttactaaaa atacaaaaat tagctgagcg tgatggcgtg 122520 cgcctgttgt cctagctacttaggggcctg aggcagaagg atcacctgag ccttgggagg 122580 tcgaggctgc agtgagctgtgatccactgt actccaccct gggcagggca gtagagtgag 122640 accctgtctc caaaaaaaaaaaaaacaaca aaggtaattt gttatttgta tccttaagca 122700 aatgctaaag gggtaacttggggatagaga aaagtccaca gatgttaggg tttgaagaca 122760 ctaatagtat ctaggccagtggttcctgaa cattagtctg tgggctcttg ctgggctgtc 122820 tgcataggaa tcacctgagagcttattaaa aataggtttt caggctggtt gcggtggctc 122880 acgcctataa tcccagcactttgggaggct gaggcaggcg gattacttga ggtcaggcgt 122940 tcaagaccag cctggccaacatggtaaaac cccgtctcta ctaaaaatac aagaattagc 123000 caggcatgat ggcacacacctgtaatccca gctactcagg aggctgagga aggagaattg 123060 ctcgagcccg ggaggtggaggttgcagtga gcggagatca tgccactgca ctccaggctg 123120 gctgacagag ggagactctgtctcagaaaa aaaaaaaaaa ataggttttc agtctgggta 123180 ccggtggctc acacctgtaatcccagcact ttgggaggcc aaggcaggca gatcacttga 123240 ggtcaggagt ttgagaactgcctggccaac atagtgaaac cttgtctcta ctagaaacta 123300 caaaaaatta actgggcattttgacgggtg cctataatcc cagctactag ggaggctgag 123360 gcaggagaat tgcttgaacccgggaggcag aggactgcat ctcaaaaaaa aaaaaaaaaa 123420 aaaggtttcc agtccccctgtctcagaaat tctgattctg caggtttgag gtgtgaccag 123480 gaatctttat ttttagaagacataccagat aattctgata aatagccagt ttagggatgt 123540 agtctaattt tcctattttgcaagtaagga aaataaggcc cagagaggta atgattttct 123600 caaagtcaca gaacaagttagtggcagaat ttggactgga atgcagttct taatgttctg 123660 tccagtgttt attctggtacagtatgtttg tagaaggtat tacgtaagaa acattgttat 123720 atagatgttg agataggaagagtttacatt tagaaatttg gtctaaaatg cctgaacatt 123780 caagtcgtgg aggagtattgaccaacttac tcaatacaac ataggagatt cacattttgt 123840 tacaaaaatg ctgatttaaaaggagagttt tctttttttt cttctttttt attttttgag 123900 atggagtctt gctctgtcacccaggctaga gtgcagtgac acgatctcag ctcactgcaa 123960 cctccacctc ctgggttcaagcggttctcc tgcctcagcc tcctgagtag ctgggattac 124020 aggtgggggc caccacgcccagctaatttt tgtattttta gtagagacag ggtttcacca 124080 tgttggccag gccggtcttgaactcctgac ctcaagtgat ccacccacca ctgcctccca 124140 aagtgctggg attataggcgtgagccactg tgcccagcct gcttgttttt gtatcatata 124200 tatgcatcat cataatcatgcattatcaac ctttgtattt ctgtcaggac atagaaacca 124260 ttagagtgct tggaagagagcctttttttt tttctcgcat ttaatgcttt ttttggtatt 124320 catttcataa tcagcttaccaaaacattac ctgcattata ccccatcaag gtagaaatct 124380 ttgtgttatc aatattggttactccctttc cacaccgagt catcagtaag tcctgttcta 124440 tccaaatagg tcatatgcatctagctcacc cctcagtgct gttttgtttt gaatttgtac 124500 atgtttactc ctgatgccttgtagttatga tgatgtgttc ttattttatt ctgtgcatac 124560 aagttctcag ctcgctttttagggaaaatg accatgtctt cctttcctat aaattccttt 124620 ctatctatca agtcctcaacagagaatagg tacccataaa tatgtgattg ttagtttctt 124680 tgcctcagtt gtagtctgatccttacagct tttaaacaac agtagagttc accgtcaaga 124740 actaaggatg gttggcaggcagatagaaag gtagcaagtt gacccaacta tctctgggga 124800 agtgggaaca aagaaaggttacatcagcac tgtcatcaca tagctctata gttctaggcc 124860 tgcaggctca atcaagtagccttgtataag attctctgga ggaggtgctg aaagttgctt 124920 atacttgcta tggaatttgattttacttcg gatatctttt taccataggt acttctccct 124980 ccaagccaca catcctcttggatttgatga tgttgtacga ttagaaattg aatccaatat 125040 ctgcagggaa ggtgggccactccccaactg tttcacaact ccattacgtc aggcctggac 125100 aaccatggag aaggtaacccagaacttcaa acgtatcaaa ctacaagaag ttttattggt 125160 agaactcata aaatataaggtgggaaaacc aagcagaata gcacagtgga aattgaagca 125220 gtccagcaaa gtgattaagagcagaggcct tgagtctggc ctggtatgta cagtcacgtg 125280 ccacataaca ttttagtcaacagtggactg cgtgtacgat ggtcctgtac gattataatg 125340 gatcaaagct ggtagtgcaataataacaaa agttagaaaa aataaatttt aataagtaaa 125400 aaagaaaaaa gaaaaactaaaaagataaaa gaataaccaa gaacaaaaca aaaaaaatta 125460 taatggagct gaaaaatctctgttgcctca tatttactgt actatacttt taatcattat 125520 tttagagtgc tccttctacttactaagaaa acagttaact gtaaaacagc ttcagacagg 125580 tccttcagga ggtttccagaaggaggcatt gttatcaaag gagatgacgg ctccatgcgt 125640 gttactgccc ctgaagaccttccagtggga caagatgtgg aggtgaaaga aagtgttatt 125700 gatgatcctg accctgtgtaggcttaggct aatgtgggtg tttgtcttag tttttaacaa 125760 acaaatttaa aaagaaaaaaaaaattaaaa atagaaaaaa gcttataaaa taaggatata 125820 atgaaaatat ttttgtacagctgtatatgt ttgtgtttta agctgttatg acaacagagt 125880 caaaaagcta aaaaaagtaaaacagttaaa aagttacagt aagctaattt attattaaag 125940 aaaaaaattt taaataaatttagtgtagcc taagtgtaca gtgtaagtct acagtagtgt 126000 acaataatgt gctaggccttcacattcact taccactcac tcgctgactc acccagagca 126060 acttccagtc ttgcaagctccattcatggt aagtgcccta tacagatgta ccatttttta 126120 tcttttatac tgtatttttactgtgccttt tctgtatttg tgtttaaata cacaaattct 126180 taccattgca atagtggcctacgatattca ttatagtaac atgtgataca ggtttgtagc 126240 ccaaaagcaa taggttgtaccatatagcca aggggtgtag taggccatac catctaggtt 126300 tgtataagta cactctgtgatgttagcaca atggcaagca gcctaacgga aattctgttt 126360 attgattgat tgattgattgattgattgag acagagtttc actccattgt ccaggctgga 126420 gtgcagttgc acagtcttggcacactgcaa cttctgcctc ccaggttcaa ccaattatcc 126480 tgcctcatcc tcccaagtagctgggattac aggcaggcac caccatacct ggctaatttt 126540 tgtattttag tagagacagggtttcaccat tttggccagg ctgttctcga actcctgacc 126600 ttaagtgatc tgcctgctttggcctccgaa agtgctggga ttacaggcat gagctaccat 126660 gcctgggcag taactgaaattctctaatgc cattttcctt atctgtaaag tgacgataat 126720 atgcacgttt acctcaaagttactttgatg attaaagtaa ggtaatgtat ataaaataca 126780 tattaacata gtacctgacacatggtaagc atcaaaaaat gttaactact tttattacta 126840 ttattattac gtatttttaaataattagag agcagtatca aaaattagct gggcgtagtg 126900 gcatgcacct atagttccagctactcagga ggctgaagct ggaggattgc atgagcctgg 126960 gaattaaagg ctgcagtgagccgtgttcat gcccctgcac tccagccttg gtgacagagc 127020 aagaccctgt cttgaacaattaaagaaggc attatgccgc aacgttagct tagaaatgat 127080 ccacatatat caccagtaactgtcaacagg attggaaccc tagttttggg tattatgatc 127140 acaaggtatt attaatagcttattaataat aaagcgttgg ctaggcacgg cgactcacat 127200 ctgtaatccc agcactttgggaggccgagg tgggtggatc acctgaggtc aggagtttga 127260 gaccagcctg accaacatggagaaacccca tctctactaa aaatacaaaa ttagccgggc 127320 gtggtggtgc atgcctgtaatcccagctac ttaggaggct gaggcaggaa aatctcttga 127380 acccgggagg cagaggttgcagtgagctga gatcgcacca ttgcactcca gcctgggcaa 127440 caagagcaaa actccgtctcaaaaatataa ttataataaa taaataaaag taaagtattg 127500 atgtttgtga atgatttattcttctaatga actagaggag atttttccag gaatttcaga 127560 gccagtgagg ttatgttgcttgtatgtgtc atgtgtatcc aggtgaaaaa acttaattaa 127620 acgctattat ataataccatacataaaaac tgaattttag gaatactgaa gaatgacata 127680 tagaagtcaa atcattaaatagctagtagt aaacagaata gagtgtcagc tgttacccaa 127740 tgatgataat attttcacgattaaaattaa accttttctg attttaaagg aaaagttcag 127800 atctgtatca tataaagaatgtaaattttc agggtaataa aattaaaatg cagagagaaa 127860 aatgcaaaaa tagttcttactagatgtgtg tatgtaagga acttagacta attttaagaa 127920 cactgtcaag accctggtagttaggtagga aaaaagacat gaatgattca ttcaacaaaa 127980 actttgagta tttctgtgctagatggtagt gttacagtgg taaacaaaat aaatgtgttt 128040 ctgctatcct ggagcttagtctacaaaaaa ggtacatatt ggccgggcac ggtggctcac 128100 gcctgtaatc ctagcactttggaagatcga ggcgggtgga tcacctgagg tcaggagttc 128160 aagaccagct tggccaacatggcgaaaccc cgtctctact aaaaatacaa aaattaactg 128220 ggtgtggtgg cggacacctgtaatcccagc tactcgggag gctgaggcag gagaatcact 128280 tgaacctggg agacagaggttccagtgagt cgagatcatg ccactgcatt ccagcccggg 128340 ggacaaaagc gaaaatacgtctcaaaaaaa caaaaacaaa caacaaaggc acgtattaaa 128400 tacgaacata aatatttacaaattatactg aataagttct catgtttatt atttgcttgt 128460 ccagttacaa acttttccttcgtagaatta gaaatataaa taataaacat gagaactcat 128520 tcagtataat taataattattaaatgtaaa taaaaacatc tatgtacaat taggcattta 128580 tttaagaatt atttgaaaaaaaaacaatgt ggaaacagat attttgatat attgctagtg 128640 attgaaattg ataatgttcttttgaagagt aaagtgacca tatatattaa agttaaaatt 128700 taactcagca atcacacgcctggtgagtta tcttaaggaa atcagtttga aagtaaaatc 128760 aatatatgca caaagactttaacatttatc ataaaccaga aaaatcgagt ttcaaattat 128820 atcctatgga ctattttctgctaaaaagta ttaatatcaa ctttatgtaa tactttcgtg 128880 acaaatattt tgggggagaaaacccaacaa aattacatgc attgtaattt tttttttttt 128940 ttttttttta gacagtcttgctccagcgtc caggctggag tgcagtggtg caatctcggc 129000 tcactgcaac ctccatctcccaggttcaag caattctcct gcctcaggcc tcccgagtag 129060 ctgggattac aggcgctcaccaccatgcct agctaatttt tatagttttt agtagagatg 129120 gggtttcatc atgttggccaggctggtctt gaactcctgg tctcaagtga tccgtctgcc 129180 tcggcctcct agagtgctgagattacaggt gtaagccact gcacccagcc ttatgcatta 129240 taattttaat ttgtaaactgtacaaaggga taatacttgt agtacaacaa gaagtaaaaa 129300 catttgttat aggtagttaacatttgtaac cagtagaatt ataggtaaaa tttatttatt 129360 taaaacagtt ttagttggatttgatttcaa ctttaaaata atgcttttca tctctatcag 129420 gtctttttgc ctggctttttgtccagcaat ctttattata aatatttgaa tgatctcatc 129480 cattcggttc gaggagatgaatttctgggc gggaacgtgt cgctgactgc tcctggctct 129540 gttggccctc ctgatgagtctcacccaggg agttctgaca gctctgcgtc tcaggtattg 129600 actgattgcg tctgccattagggagaaaag catacacatc ctttccttca catcccagta 129660 acagatccta ttatttgtaaattttaagtt gtggaaaaaa aagataaaag ccaggcacag 129720 tggcctgtgc ctgtaatcccagcactttgg gaggctgcgg tgggcggatc acacgaggtc 129780 aggaattcga gaccagcctggccgacatgg tgaaacccca tctctactaa aaatacaaaa 129840 attagccggg catggtggcaggcacctgta atcctagcta cttgggaggc tgaggcagga 129900 gaatcgcttg aacccaggaggcagaggttg caatgaacca aaatcacgcc actgcactcc 129960 agcctgggtg acaaagtgagactgtgtctc aaaaaaaaaa aaaaaagaga gaaataaaat 130020 tagcctactt actatcttctaatcaaagca tttgtggtaa cttaaaatat actgtattgt 130080 aaagtatcat gctgtttcatttaggccatt attctatttg aatctgtggc tgtttctctt 130140 aataaatcaa gtaatatggaatatattcat agcctctgaa gagctcttta tgtaagtatt 130200 tatttaggat actttttgtaaaataagtga atgaattctt aggtctcctt tttttttctt 130260 ttcttgagac agggtctcctcgctgcaacc tggaaattct gggctcaaat aatccaccca 130320 ccacagcctc ctgaatagctgggactagag gcatgcacca ccacgcctgg ctaatttgaa 130380 attttttttt ggccaggcatgatggttcac gcctgtaatc ccagcacttt gggagaccga 130440 ggcaggcaga tcacgaggtcgggagatgga gaccagcctg gccaacgtgg tgaaaccccg 130500 tctctactaa aaatacaaaaattagctggt tatggtggct catgcctgta atcccagcta 130560 cttgggaggc tgaggcaggagaatggcttc aaccagggag tcggaggttg cagtgagccg 130620 agatcacgcc actgcactcctgcatggtga cagagtgaga ctccatctca aaaaaaattt 130680 tttttttaaa tgatggagtcttgctgtgtt gctcaggctg gtcttgaacc cctgacctca 130740 aatgccgcct gcttcagcctaagtttcttt tttttttgta aagagacagg gtcttgctat 130800 gttggccagg gtagtctcaaactcctggct tcaagcagtc ctcccacctt ggcctctcaa 130860 agtgctggga ttacaggcgtgaaccactac ctataatgtt gtgtttcact caaggccttt 130920 tgatttcgtt ttgcattaccgtgccacatt gtgcatttcc ttgacctttt ttgggttttt 130980 tggagtgctt tcatatgttaaaccatacct gattctcctc aaaatcacac aaagtagaat 131040 atcctaagac aagaaatctaaggaggcata aagaagttaa ctggttttat taaactcaca 131100 cagtaaatga tagagccagaaatattcccc ttctagtgtt cttcaccatc agcttaatgt 131160 agcataataa ttttctaattactgttgaca aataaataac cctttgaatt ttcaatactg 131220 ggccttggat aaattttcctaatttgtaag agagtattat cgtattgcca tttacaaagc 131280 tctcctgagt atctttttcttctgttaagt ttacctagga gataaactgc tgagtatggt 131340 tgccattttg gttttttgatataggttaga atgtcttggt tttttttttt tttttttttg 131400 gtttttgttg ttgtcattgtttgagacagc atcttgctct gtcgcccagg ctggagtgca 131460 atggcacgat cgtggctcactgcaacctcc acctcccggg ttcaagcaat tctcctgcct 131520 cagcttcctg agtagctgggattacaggca tgtgcaacca cacctggcta atttttgtgt 131580 ttttagtaga gaaggggtttcaccatgttg gtcaggctgg tattgaactg ctgacctcat 131640 gatccacctg cctcggcctcccaaagtgct gggattgcag gcatgagcca ctgcacctgg 131700 ctgaatgtct tgtttttgattaggcactta agaaaggcct aggtactaac cataaaatat 131760 atttttatac cttttgttgatactatatat atagaaaact gcacttatca taaccttaga 131820 caccttgaag aatgttcacaagcagaacta acccatgtga cccagcatcc agatcaaaaa 131880 cagcattatc agcccctctagaagccctct tgggcccctt ccattcactg tccttcttgt 131940 caccagggta gctactatcctgacttttga tggcatagat tagcattacc tgttcttgtc 132000 attttataaa taaaaccatactgtgtattc ttttcttgta cagctttatt gtgctaattc 132060 acatttacat catacaattcagtggttttt atatggtcac agagttaggt aaccattacc 132120 acatcgattt tagaacatttttttcactcc agatagaaac cccctttact taaactccaa 132180 atcccccact ccaccagccctaggcagcca ctagtctact ttttatctct atagagacaa 132240 tagatttgct tattctggacatttcataaa catggaaccg tatattatgt ggtcttttgt 132300 tgccaactgt ctttcacttagcatcatgtg ttcaaaagag catcatgtta tccatgtttg 132360 gcatgtatca gaattttattcctcattatg gccaaatatc ccattgcaag gatttatgac 132420 attttatttg aattgtaccctcctttctgc catttatcaa taatgctact gtgaccattt 132480 gtgtacaagt ttttgtgtggatacaggttt tctttttgtt tttaaatttg aggtggagtc 132540 ttgctctgtc gcccaggctggagtgcagtg gcacaatctc ggctcactgc aacctctgtc 132600 tcctgggttc aagcagttctcctgcctcag cctcccgagt atctgggact ataggcacgc 132660 accaccacgc ccagctaattttttagtaga gatggggttt caccatgttg gccagtctgg 132720 tctcgaactc ttgacctcaagtgatccacc catctcggcc tcccaaagtg ctgggattac 132780 aggggtgagc cactatgcccggctgtggtt ttcatttctt ttgttgtata tacataggag 132840 tagaattgct gagtcaagaggtaactctta aacttattga aaaactgcca gattgttttc 132900 cgaaaaggct gcaccattttgcaatcccac cagcagtgta tgagttttac agcttctcca 132960 catttcattg gaacttattatctgtttggc tgtttttaaa aatgatagtc attccaataa 133020 gttctacttc agtgtggtttttgcacttct ctgatgagta atgatgttga gcatcttttc 133080 atttgcttat tggcctttgttctagctttg gaaaaatgtt tattcaaatc ctttggccat 133140 ttttattttt atttttatttatttattttt ttttgagacc aagtctcact ctgtcagcca 133200 ggctggagta caatggtgtggtctcagctc actgcaacct ccgcctcctg tgttcaagtg 133260 attctcctgc ctcagcctcccgagtagctg ggattacatt tcaggcacct gccagcatgc 133320 cgggctgatt tttgtatttttactagtgac agggtttcac catgttagcc aggctggtca 133380 caaactcctg acctcaggtgatctgcctgc ctaggcttcc caaagtgctg ggattacagg 133440 cgtgagccat tgggcccagcctagattttc ttttttcttt ttttttttga gaaggagtct 133500 tgctcttgtt gcccaggctggagtgcaatg gcacaatctt ggctcactgc aacctctgcc 133560 tcctgggttc aagcgattttcctgcctcag cctccccagt agctgggatt acaggtgcct 133620 accaccacac ccagctaacttttgtatttt ttttagagac agggtttcac catgttggcc 133680 aggctggtct caactcctgacctcaggtga tccacctgcc ttggcctccc gaagtgctgg 133740 gattaccggc atgagctaccaggcccagcc aattttctca ttatattgcc caggctggtc 133800 tcaaactcct gggttcaagtgatcctcctg ccttggcctc ccaaagtgtg gggagtacag 133860 gcgtgagcca ccttgctcagcccctttgcc catttttaaa ttagattgcc tttttatatt 133920 gagtttcagg agtcctttatatattctaga taaatgtccc ttatcaaatt atattatttc 133980 caggtatttt cttcattctgtgagttgtct ttcctctacc ttttaaaaaa ggtgggtttt 134040 tgtttgtttg tttgtttgtttttttaagat aaggtctcat tctgctgccc aggctggagt 134100 gcagtggcac aatcacagctcactgccacc tcaacttcct gggccgaagt gatcctctta 134160 cttcagcctc ctgaatagctagggccatag atacacacta tcacacccag cttttttttt 134220 ctgtttgtag agacagatcttactgtgttg cccaagttgg tctcaaactc taggctcaaa 134280 gtgattctcc cacctctgcctcccagagtg ctgggattac aggtgtgagc cacacgcaac 134340 ctgtcttttc actattaatagtgtcttcct gcttcagcct cccgagtagc tgggattaca 134400 ggcacccacc accatgcctggctaattttt ttgcattttt agtagagaca gtgtttcacc 134460 atgttcaccc ggctggtcttgaactcctga cctcaggtga ttcacctgcc atggcctccc 134520 aaagtgctgg gattacaggcgtgagccact gcacccggcc aaaatattgc cttcttaaca 134580 gtattgtctt ctaatttgtgaacatggatg tatcttcatg tatttatgtg ttctttcatt 134640 tcagcagaat tttgtagttttcagagtaga agcctttcac ctccttgggt catttattcc 134700 tatgttttaa gttcttttcgattccattat aaatagaatt gttttcttaa tttcattttc 134760 agattgtttg atgagagagcatagaaatac aagtgatttt tacatgttga tcttgcaact 134820 tcaactttga taaatctgattgttagctct aatagttttc ttgtggattc tttaggattt 134880 tcaatatata agatcatgtcatttatggat agagatagtt ttttttctgg ctagaactta 134940 cagagcaatg atgagtagaagtggcagaag caaaaatctt tgtcttgttt cctatctgac 135000 agggaaagct ttcagtttcatcatttaata tgatgttagg tgtgggtttt caataaatgc 135060 cttttttcag attcaggaatttccctatca ttcctgattt tttaaggctt tttttttttt 135120 ttaaatcatg aaagggtgttgaatattgtc atgttctttc tgtatcagta taaatgatcc 135180 tatggatttt gggttttattctgttgatgt gaaatattaa ttgattttca gatgttaaac 135240 caaccttgca tacctgagatgaatctcact tggtcatggt gtataatctt ttcaatatgc 135300 tgctggattc catttactggtattttgttg aagattttgt atctgaacgc ttaagataac 135360 atttacactc tatcagaaatgaattgacca taaatgtgag agtgtatttg tgggttcttg 135420 attctcttcc attccaaagatagacataca tccgtctgta tgtctgtctt tatgccagta 135480 ccatactctc ttgattactattgctttgta ataagttttg aaatcagaaa gtataaatga 135540 gattttggta tctgagtaacagtcctcata gaattagttg ggaaatattc cctctttatt 135600 ctggtccctc tttcttttttgtttaactgt gtatcttgga gattgttcct tctcaacaca 135660 tgagagccgc tttccctaccctcccacccc tgctatagag aggtctataa gtgtctgttc 135720 aattatttta tttacttaacctattactta gtcggggaca ttaagcttgt ttatgtcttt 135780 tattttaaac aatgctgcagtgaataatct tgtatataag tcattttcca tcaatataag 135840 tctctctgta actgaatttttagaagtgga atttctaggt caacctatgg ctctgtattt 135900 cacaaaaata ccaattctggtttttcttgt ggaggtgggg agtaggaggt agaatgctgg 135960 aggagaactt gctgtactcagctggctagt cattttagaa aggtttcctt agcttctttt 136020 tgtcatatgg cctcaccaagaatcaaaaac attcctattt accctgtaaa catggggctt 136080 tactacccaa gatacatatttctggatgta tgacagcttt tcatattgaa gaaataatgc 136140 tgtgagtaca gcacatttgttggaacttag gtcgttaaga atgtcttata aattcataca 136200 ttatacattt tattttattttattttttag tttttgatac agagtcttcc tctgtcgccc 136260 aggccagcgt gcagtggtacaatcttggct cactgcgacc tccatctcct gggctcaagt 136320 gattctcatg tctcagcctccagagtagct atggttacag gcatgcacca ccatgcccgg 136380 ctaatttttt tatttttagtagaaactggg tttcaccata ttgaccatgc tggcctcgaa 136440 ctcttggcct caagtgatcggcctgcctca gcctcccaaa gtgctgggat ccttgtattg 136500 ggtaaaagat gaatattgagggctgcatgg tggctcatac ctgtaatccc agcactttct 136560 gagactgagg tgggaggagtcctggagccc aggagggtga ggctgcagtg agttgtgatc 136620 gcgccattgc acttcaacctaggaattata ggcttcagtc actgtgcccg gcatgtacat 136680 tttaatattg tgctttcctcttttagctat agtatgaggt tacatttcag agtcattgtt 136740 gttaagcatc ttaatagtgatgaggttgag tgaaagttac ttctatttca aacactgaag 136800 aaaattttgt acaaatctgtcacattccaa gcccaggact gattgtttca tatacttcta 136860 attttacaat ttctattgtagtccagtgtg aaaaaagcca gtattaaaat actgaaaaat 136920 tttgatgaag cgataattgtggatgcggca agtctggatc cagaatcttt atatcaacgg 136980 acatatgccg ggtaagcttagctcatgcct agaattttta caagtgtaaa taactttgca 137040 tcttttaaat tttttaattaaattttacat ttttttctaa tctattatta tatgcccaga 137100 actttcactt agagtgtgcagtataatgtg gtggttaagt ataaaggctc tggagtgact 137160 tcctgggttt taatcttggctctgccattt attggcagcc gctaacctct tggtatctca 137220 gtttcttcat ctgtaaaatgagaataataa agtgaaaaga tgccaacatc atttactctg 137280 ggctgcataa ctgatacttggaaaaagtat tcctttgagt ttaagaatta agttggttat 137340 tcattttagc ttgtaataaaaagatagtga ttcataggat atgccactta ctgaaattta 137400 ccacagatcc aatcataaaatcactttctc ttccctaaag atagcttgat taacatgtaa 137460 aggtgtgtaa aggcttgattacactaccct gatccgtacc ccagttccca gcagcaccat 137520 gaaaaaggga tttcaacatatttaattact ttcagtagaa agtaacagtg gtaggccagg 137580 cgcagtggct cacacctgtaatcccagcac tttgggaggc cgaggtgggc ggatcacgag 137640 gtcaggagat tgagaccatcctggctaaca cgatgaaacc ccgtctctac taaaaataca 137700 aaaaattagc cgggcatggtggcaggcacc tgtagtccca gctacttggg aggctgagac 137760 aggagaatgg cgtgagcccgggaggcggag cttgcagtga gcttagattg tgccactgca 137820 ctccagcctg cgcagtggagcgagactctt gtctcaaaaa aaaagaaagt aacagtggta 137880 ttgggagact gaggagcctagaaagtactt gaaggaagta aaaggtttgt ttgaccacat 137940 tgtatttgga aagccagctttttcagctgt gtcagctttg tgtagtgatt tttagttctt 138000 cttttagaaa ataacggacaaggccgggca cggtggctca cgcctgtaat cccaccactt 138060 tgggaggccg agacgggcggattacctgat ctcaggagtt cgagaccagc ctgggcaaca 138120 tggtgaaacc ccgtctctactaaaatacaa aaagttagcc gggcgtggtg gcgtgtgcct 138180 gtagtcccag ctactccggaggctgaggca ggagaattgc ttgaacccgg gaggcggagg 138240 ttgcagtgag ccaagatcacaccattgcac tgcagcctgc gcgacagagt aagactctgt 138300 ctcaaaaaat aataataaaataaaaaagaa tggacagtaa acctaaatga gttcattccc 138360 aaagatgatg ttattcttaagggatggttc atttatttaa gaccttacat aaagtctatc 138420 aattgcgtga tttttcacttctgtaattgt gtgtatgtat aatgtaaata tatatgtttt 138480 tgttttgttt tggttttttgagacggagtc tcgctctgtt gctcaggctg gaatgcagtg 138540 gtgcaatctc agctctctgcaacctctgtc tcccaggttc aagcgtttct tctgcctcat 138600 cctcccaagt agctgggactacaggcacgt gccaccacgc ccggctaatt ttttgtattt 138660 ttagtagaga tggggtttcaccgtgttagc caggatggtc tcaatctcct gacctcgtga 138720 tccacccgcc ttggcttcccaaagtgttgc tattacaggc atgagccacc acacccagca 138780 tgtatttttt aaatgtataaaatgaagcag aaaagagaaa tgataatttt tcttcatctt 138840 gaaagattat cttcaccaggcgcagtggct cacacttgta atcccagcac tttgggaggc 138900 ctcggcaggc ggctcacttgagttcgaaac cagcctggcc gacatggtga aactccgtct 138960 ctactaaaaa taaataaataaagatggttt taatatatgt tttagtttta tgattttagc 139020 atctttctga aatttttctcaaggcaagta aatttgtatc agttggtata ttggtaccca 139080 tctatgaaat aacttattaggaagatatct ctaaaataag atcactttgc ctaaaataaa 139140 ctgatatatt gatgttcacagaatttttct tttaaccgac ttgataaatg cattattctt 139200 gacgtcaagt gatccaccttcctcagcctc ccaaagtgct gggattacac acatgagcca 139260 ccgcacctgg cattattcttataaaaggtt aaatttctag ttaagtttaa tgtcctcttt 139320 gttcatgtac cattgcttattttcttccct tcctactcac agtaatcatt cttatggtat 139380 gcacttttgt ttgcttatttttatgtaatt gatattacgc tccattctgt acgttgtact 139440 ttcattcaca gtgagttttggacattccta tgttcatcta tacagactta cttcatttta 139500 actacactgt agtattccgtatgtaatatt tactataact catcactgta gcagagcatc 139560 tcatagtgta tgtattactgttttgccatt ttggtatcaa tgagtattta agtcatttgc 139620 agtttttccc tcttatacccagtattacag aggatctctt tttatatgct tctttgtacc 139680 aagaggcaga ttaaaaaatttttttttgaa aaaatttttg aaaaaaaatg aaatgaagtc 139740 tcactatgtt gcccaggctggtctcaaact cctaggctca agcaatcctt ccatcttggc 139800 ctcccaaagt gctggggttacaggcatgag ccaccatgcc tggcctacat tttaaatttt 139860 gatagctctt acaatttactttgtaaagta tctgcatcat tttatgttct caccagtctt 139920 taataagaat acttcatacttttggctgga cacagtggct cacgcctgta atcccagcac 139980 tttgggaggc cgaggcgggcagatcaagag atcgagacca ccctggccaa tatggtgaaa 140040 ccctgtctct actaaaaatacaaaaattag ctgggcgtgg tggcgcaccc gtagtcccag 140100 ctactcgaga ggctgagacaggagaatcac ttgaacccgg gaggtggagg ttgcagtgaa 140160 cttagatcac accactgcactccagcctag caacagagtg agactctgtc tcaaaaaaaa 140220 aaaagaatac ttcagacttaattttttttc cagtcttaag tgtttgctaa tgagattgag 140280 tttcttttgg tatgtctcttgattgttcag gttttttctt ttatgaattg actgttcatc 140340 tctttttcac attatttctgttgggtgatt ttattagtga cttgttaaaa ttctgtatat 140400 tttttcagca tgacacttcattattcaaaa aaaaaaaaag attctctatg tttctcgata 140460 ctaatcattg gttggtaataccttaaaaat aagaccctta ctgtattttt tgcttttttt 140520 tttttttttt tttttttttttttgagatag agtcttgctc tgttgcccag gctggagtgc 140580 aatggtatga tctcggctctcagctcactg caactgcaac ctctacctcc ctgtttcaag 140640 caattctcct gccttagcctcccaagtagc tgggattaca ggcatccacc accacaccca 140700 gctaattttt gtatttttagtagagacagg gtttcaccat gttggccagg ctggtctcaa 140760 actactggcc tcaagtgatccgcctgcctc ggcatcccaa agtactggga ttacaggcat 140820 gagccacagt gcctagccactttttgcttt ttaactttgt tttatagtac tatagtttta 140880 gtataaacag atgtatgtatacacacaact atggctttat aatatgtttc agtcattgtt 140940 agagcaaggc ctaccttttgggtgcttctt ttacaaaatt gtcttggcta ttcttgtgcc 141000 ttttttctta tttgtgaattttagaattgt gaattacctg ttgactcacc atgttttgta 141060 aactgaggat tttgaatggaattgcactca attaaagatt atcttgcttt ctgtgcagca 141120 atgttttatt tcaaataatccctactttaa attacttagg atagctataa attgtgtttc 141180 tggctttcta gatttagatgaaacgcttta aattgattgt tttctcctaa atttaaaact 141240 gattgttaga agttaaagtcttctgttcat tcttatttag gaagatgaca tttggaagag 141300 tcagtgactt ggggcaattcatccgagaat ctgagcctga acctgatgta aggaaatcaa 141360 aaggtttgtg gtgtttttatacttcatatt aagcctttac tcacattagt gattgactgt 141420 aagtcaaaga ccacttaaggtttaaactgt ttattttgta aagtaaccac tgtatctttc 141480 accttgtgtt tatagtcagaagtaagtaca agggcttcct gtagtcacat ctttatgcaa 141540 tctcctctga atcaaaagttagtgaacttg ctttgccact ccagaaggca catgaatatg 141600 aaaaagcatt gtctattttcttatttaatg gcaaaatacc cgacctaagt tggacttaat 141660 gtttgagacc gtttattttattaaattata ttttttctct tttctttttt ttttttgaga 141720 cagttcttgc tctgtcacccagaccggagt gcagtggtct gaccgcacct cactgcaacc 141780 tctgcttcct aggttcaagcgattttcctg cctcatcctc ctgagtagct gggactacaa 141840 gtgcgcacca ccacacctggctaatttttg tatttttagc agagatgagg tttcaccacg 141900 ttggctaggc tggtctcatactcctgacct caagcaatcc atccgccttg gcttcccaaa 141960 gtgctgggat tacaagtgtgagccaccatg cctggcctta ttaaattatt tttattaaat 142020 ttcctcaaga ttgatgaaagtaatgaaata taaaagtaat gaaatatatg tggaaaatag 142080 actggattaa gaaaatgtggcacatataca ccatggatac tatgcagcca taaaaaagga 142140 tgagttcatg tcctttgtagggacatggat gaagctggaa accatcattc tgagcaaact 142200 gtctcaagga tagaaaaccaaacaccgcat gctctcactc ataggtggga attgaacaat 142260 gagaacactt ggacacagggtggggaacat cacacgctgg ggcctgtcgt ggggtggggg 142320 gctgggggag gaatagcattaggagatata cctaatataa atgacgagtt aatgggtgca 142380 gcacaccaac atggtacatgtatacatatg taacaaagct gcacgttgtg cacatgtacc 142440 ctagaactta aagtataataaatttaaaaa aaataaatat atgtggaaaa tattaatagg 142500 tcaaaattca aattgttcatttaatcagaa gagtagttta gtcaaatcca agggttagac 142560 aacagaaatc ttttttgtcaagtgcattct ttgtgactga tttcattttc ttcctggttt 142620 acacaggaag atttcagaaacaaatgtgga tccgtgacag atggtatcta gaagttttta 142680 gtttggttga attgacagtattttattgag taaaagatac taatttttgt aagaagaaaa 142740 attcaatttt gataagtatgtttaagatta agagctattg gccaggcgct gtggctcatg 142800 cctgtaatcc tagcactttgggaagctgga gcaggtgggt cacgaggtca agagattgag 142860 accatcctgg ccaacatggtgaaaccctgt ctctactaaa ttagccaggc gtggtggcac 142920 atgcctgtgc acccgcctccgggtttaagc gatcctactg cctcaggctc ctgagtagct 142980 gggattacag gcgccatggctaatttttgc atttttagta gagacagggt ttcactacat 143040 tggccaggct ggtctggtctcaaactcctg acctcaggtg atctgcccgc cttagcctcc 143100 caaagtgctg ggattacaggcatgattcac catgtctggc catttatctt attttctttt 143160 tttttttttt ttttgtttgagacggagtct tgctgtgtcg cccagagctg gagtgcaatg 143220 gtgcgatctc agctcactgcaacctctgcc tcctgggttc aagcaattct cctgcctcag 143280 tcttccaagt agctgggattacaggcgcgt gccaccacat ctagctaatt tttgtatttt 143340 tagtagagac agggtttcaccatgttggcc aggctggtct cggaactcct gacctcgtaa 143400 tctgcccacc tcggcctcccaaagtgctga gattacaagt gtgagccact gtgcccagcc 143460 atcttatttt ctttctttttttttgtcggg tgggaggggg acagagtcta gctctgtcgc 143520 caggcttggc tcactgcaacctctgccccc caggttctag caattattct gcctcagcct 143580 cccaagtagc tgggattataggcacctgcc accacgcctg gctaattttt tgttattttt 143640 agtagagatg gggttttgctatgttgacca tgctggcctc aagtgatccg cccaccttgg 143700 cctcccaaag tactgggcttacaggcgtga gcttgtattg ggtaaaagaa caatattggg 143760 ggctgcatgg tggttcatacctgtaatctg agcactttgt gagactgaga tggaaggagt 143820 gttggagccc aggagggtgaggctgcggct gcagtgaatt gtgatcacgc cattgcactt 143880 ccacctaggt aatggagcaagaccatgtct ctaaaaaaca aaacacaatt tttttaagga 143940 atactgggaa gaggtcagtggtggttttag aacagaggaa gtgccagatg acctttgtga 144000 ggcattggcc aggaagaactctacagtgtc tttaggtagc ttctgtccat aaggataatg 144060 gggtctcctc cccagtattaatagaaaatc tctgagctgt ttttttttgt ttgtttgttt 144120 tgtttttttt tcctgagatggagtctctct ctgtcggcca ggctggagtg ctgtggcgcg 144180 atcttggctc actgcaagctctgcctccca ggttcacacc attctcctgc ctcagcctcc 144240 caagtagctg ggactacaggtgtccaccac cacgcccagc taattttttg ttatttttag 144300 tagagatggg gtttcaccatgtcagccagg atggtctcga tctcctgacc tcgtgatccg 144360 ctcgcctctg ccttgcaaagtgctggagtt acaggcgtga gccaccgtgc ctggcctggt 144420 ttttttgttg ttgttatttatttatttatt tatttatttt ttgagacaga ctctcgctct 144480 gtcgcccggg ctggagtgtagtggcacgat gtcggctcac tgcaagctct gcctgccagg 144540 ttcaagccat tctcctgcctcagcctcctg agtagcaggg accacaggcg ctcgccacca 144600 cgcccggcta attttttgtatttttagaag agacggggtt tcaccgcatt agccaggatg 144660 gtctcgatct cctgatgtcgtgatccgccc acctcggcct cccaaagtgc tgggattaca 144720 ggtgtgagcc accgtgcctggcctgatttt tttttttttt taatctggtc tcatacctct 144780 gacagctcat gaagaagtgctcctgcttca tatgtatatg tgttagcata gtgttaacat 144840 agcataggtg ttcggtgtttgcagtttctg tttgttttat atgaattaag gtgtattatg 144900 agcagttgaa gatatataggaaattttttc ccaaaccact atctctgctc gttctattca 144960 ttcagtctgt ttatgttattccttcattca ttcattttat agaacagtgg agtgcctact 145020 gtatgcatct attgttctgggtcctgggga agaaaacaaa gttcctgctt tcatggaact 145080 tacattatat tggcggagacagtaacagac aaacaaatgt agcctgtgta catgtgttac 145140 atgaaaagca gggtagggggctgggagaga gtagtaggga gtgctatttt cgaggtggtt 145200 gtcaggaaag gcctcactgaggaggtggca ttttgagtag acctgagcgc agcgggggcg 145260 taagcccagg cagcatgtggaggaagagtg ttcttggtga aaggaacaag gatagaggcc 145320 cgaagctaga gagctcagcatgatcaagga acagcaagcc ccgtgtggct ggaatggagt 145380 gagcaaagga atgagcagtagaaggtgagt gagttgggag gtcaccagag accatggcaa 145440 ggacttgaaa gtgtcagggacacattggaa gttggagcag ggaaatgatg ggatttatgt 145500 tttgtttttg ttttatgtttagtgttttta agggattgct ctatcagcta tttggaaaat 145560 ttagtgtagg gcttcaagaagagaagcaga gaaacaacat tcttgccata gtcatagtct 145620 aagtaaggga tgatggtggtgtggattagg ctggtagtgg aagaccagtc cagttcgggt 145680 tgtatttgaa ggtagaggcaaaaagattat atttctacca gcaagcccat ctatgaagtt 145740 acttgtatta ttaatttaattgagacatgc ccacataaac taataaatag gaatttctgc 145800 agtttggtta aacacccctgtatatcctgg ttcttctttt agttgtccag atgtctcttt 145860 aagtcaagta ttttttggtggtgtaggagc ctagagattg aatttattca cccaaaaggc 145920 atttgagtga ttactatgtgccaggcacta tgctgaatgc caaggatgta aataagaggg 145980 cgtagtctca gtctgttttactccagcttg gttccttttt aatgaccctg acttgttaag 146040 catatcagtt atcctacagaatgtttaatc ttctgtactt tcctggttgt gttatttagc 146100 ttatttctct ttccttgacatttcttgtaa actggaagtt acacctatag tcttgatgat 146160 tcgtgttaca cattttagattagaacacat catgtgttgt atatggtgtt tttgaaagcc 146220 tctctgtata ttggtctgtacattaaaatg ttgcctgaat ggatacacat aaaatttaac 146280 agtgattaca ttagagatgagaagaaagag gtgcctttta cttttcaata taccttttcc 146340 tctgcttttt gaactttcttgccctatgca tacgttattg cttaatcatc cacctcatct 146400 cttcccctgt ggctttctgttgcatttgga atgaaatcta gcctctttgc tgttacctgt 146460 ggatgtccct tgctggcctctatcacctta ctttgaacca ctcctttcat ggactgagct 146520 ctcattggac tatcttttattcttttgctg aagtttcttc actttgagtg cctctgcagt 146580 tgctatttca tggctgtggcaagccctgcc atggctttca tgcaaggatg gttcctcctt 146640 ctcatctcaa tattatctcttcagagaggg accttcccaa ctccgatgat ctaaaatcct 146700 ttgtatatac cactcactaccacttctttc ttttcttttc cttttatctt tttttttttt 146760 tttttttttt gagatagggtcttgctctgt tgcccaggct ggaatcacga ctcactgcag 146820 cctcatcttc ttgggctcaaatgatcctct cacctcagcc tctcgagtag ctggaactgc 146880 aggcacacac caccatacttggcttattat tttacttttt gtagagacag ggtttcacca 146940 aggctggtct caagctcctgccgcaagcaa tccacatctc tcagcctccc aaagtattgg 147000 gattatagga gtgagccactactcctggcc tattttctta ttcactgtct aaaattatct 147060 tgttcattta tttacatacttgtttatagc ttatttctca gctggacatg gtgcctcaca 147120 cctgtaatct caatactttgggaggctggg ttggagaatt ggttgagccc aggacttcaa 147180 gaccagcctg ggcaacaaagtgagaccctg tctataaaaa attgtttaaa aattagctgg 147240 gcatggtggc acatgcctgtggtcccagct acttgggagg cagaggtggg agaatcgctt 147300 gggcccagga ggttgaggcgacggtgagcc atgattgtgc cactgcactc tagcctagtg 147360 acagagtgag accatgtgtctaaaaagtaa ataaaaatag tttctctttc atgactagaa 147420 tattacctct atgtgggcagggagtttgtc tatactattt ggcactatat ttcctgattc 147480 tgaaattatg cctagcacatggtaagtact ccttaaatat ttattgactg aattatttaa 147540 tacttaagaa tttcatttgggattatctga gtggtaagat tacggattat atttatgtaa 147600 gaaaaaatca ttttttaaacttggttgccc tttgccacac tgacatagac actaagtttt 147660 cttagccaga ttacttccgaggatactcac agaggccatt ctcttctcaa tccccaaata 147720 attgatattt cttagcactttcaagctaat gcaattctta gatgatgtat ctgtgtatat 147780 catatcctca ttctacaaatgtagaaattg aagtctgggc acagtggctc tcacctgtaa 147840 tctcagcagt ttgggaggccaaggcgagcg gatcactgag gacaagagtt aagaccagcc 147900 tggccaacat ggtaaagccttgcctctatt aaaaatacaa caattagggc cgggcgtggt 147960 ggctcacgcc tataatcccagcacgttggg aggccaaggc aggcagatca cgaggtcagg 148020 agttcgagac catcctggctaacacagtga aaccccatct ctactaaaaa tacaaaaaat 148080 tagccaggca tggtggcacgcgcttgtagt cccagctatc gggaggctga ggcaggtgaa 148140 tcccttgaac ccgggaggcggaggttgcaa tgagctgaga ttgcaccgct gaactccagc 148200 ctggtcaaca gagggagactctgtctcaaa aaaaaaaaaa aaaaacaatt agccaggcgt 148260 ggtggcgggt acgagtacctgtaatcccag ctactaggga ggctgaggga ggagaatcac 148320 ttaaacccag gaggtggagtttgcagcggg ctgataatgc accactacat tccagcctgg 148380 gcaacagagt gagactctgtcttaaaaaaa aaaaaaagaa agaaagaaat tgaggaatgt 148440 ggagattgtg gtctgtgatttgttaggaat cacacagcag gttagtagca actacagggc 148500 tttggttcag aataccaccttgacaatggt ttgtttacag ttcggctccc cttcctctgc 148560 ctttctctcc ttccttattgagggcagctg gaaagaattt tcatcattta ctagcctata 148620 gctttaattt gagttttgaaaccttgataa tagagcacag aggaaaagac tgagttttct 148680 ttttttgaga cagtcttgctctatggccca ggctggagtg cagtgacacc atctcagctg 148740 gttgcaacct ctgcctcccaggttcaagca attctgcctc agcctctcga gtagctgaga 148800 ttacaggcac gtgtcaccacgcccagctaa ttttctgttt ttgtttcgtt ttgttttttt 148860 ctgagatgga gtcttgctctgtcacccagg ctggagtgca gtggtgcgat gttggctcac 148920 tcaaacctct gtctcctgggttcaagcaat tcttctgcct cagcctcccc agtagctggg 148980 actacaggta cgtgccaccatccctagttc atttttgtat gtttagtaga gatggggttt 149040 cactatgttg accaggctggtctcgaactc ctgatctcag gtgatctact cgtctcagtt 149100 tcccaaagtg ctgggattattggcacacgc ctatttttgt atttttagta gagacggggt 149160 ttcaccatgt tggttagactggtctcaaac ttctgacctc aagtgatttg cccgccccag 149220 cctcccaaag tgctgggattacaggcgtga gccaccgtgc ccagccaaga ttgagttttg 149280 aaaagagcct tctgagattatgagaagggc aagcaagata acttaagaag ttacattaaa 149340 atcatctaag agacagtgtaacaagaagga attgtaaaat gatgttatga gcacgtgccc 149400 aatgtagtgg caatcccttgtgcttcgata cattggtggg agacaaaact gtacttaaat 149460 tgataaatcc cttacatgtcattttaagga gcttagactg actcccatca tgtagacatc 149520 agagatttct tttttttttttttttttttt tttttttttt tttgtgacag agttttgctc 149580 ttgttgccga ggctggagtgcaatggcgtg atctcggctc accacaacct ccacctccca 149640 ggttcaagca attctcctgcctcagcctcc cgagtagctg ggattacagc catgcaccac 149700 cacgcctggc taattttgtatttttagtag agacggggtt tctccatgtt gtggctggtc 149760 tcgaactcct gacctcaggtgatcctcccg cctcagccac ccaaagttct gaaattacag 149820 gcgtgagcca ccgcgcccagcccagagatt tctaaacaga gttctaacca gatgcttttc 149880 cctgtcagta gaatgagaatgaattggagg tgggagagac tggcatgagg gacaccagtc 149940 agccagtgga attagctggtaatgttgata ggagaagaaa aagattcaaa gttaggtagt 150000 ggtagcaaga attagagggaaggtcggatt tatgatatgt ccaaggttga attctaaggt 150060 gaaatttggt ggcagatttcatgtgtaaat tgggaaggta gattgagttt ttttaacatg 150120 ggttttctaa catgtcaatagagtgactct gcaggggggc ctgacgagag aacagtgcat 150180 ggggtgattc aacagccagttgagccttca tgcagagcat ttaacactgt gactctgtag 150240 actctggttg gcagtaaaatttcattaaac caatatttaa acccttaggt aataataaaa 150300 attgagggaa aaggatccaggttttgtatt ttttatgaat tcagttattg aattaaacag 150360 gaccttgcct caagaaataatctaccaaca attaacttgt tttaaagcaa agttaggaag 150420 tgagcatgtt caaattattaaataaaaaag taagctgtgt atttcattca tagaaataga 150480 ggctggccta cttcggatgattctcagcat gtgattacag atgtgggctt atacatccta 150540 gggagttaag gcgtactctggcttggatag agtagagctc tttgaaactc ttctctcacc 150600 cagctagttt atatagactagagaactaga atgtagcagc atactctgtc ttagaagccc 150660 ttttatatag gagctggtctggaaggtttg aaaacataac aaatgtgttg gtgtctccca 150720 atgtattgct agattcttacccaagagcat tatcctggtt agggtttggt ttggttttgt 150780 tttgtttttt aatgtttgccacaaactaac actagatgtt agttctttca tcaagtgagg 150840 agagtagaag aaaagtccagaactctgaaa caccttttca aaagtttttc aagccatgat 150900 gtttgcaagt taaatgctctgttatgtaag caatataatc agtttttatt aatgtaacat 150960 tccttagtgt tttggggtatcacacaaaaa agaatatcca tatctggaag caacagcttt 151020 taaataagag cattgtggtggtggtggtga tagtggtttt tttttttttt tttgagttgg 151080 agtctcgctc tgttgcccaggttggagtgc agtggcacga tctcagctcg cttcaacctc 151140 tgctcccagg ttcaagcaattcttctgcct cagcctcctg agtagctggg attataggca 151200 cctgctacca tgcctggctgatttttatta ttttagtaga gacaggtttc accatgttgg 151260 ccaggctggt cttgaactcttaacctcagg tgaatcaccc acctcggcct cccaaagtgc 151320 tggaattaca ggcatgaaccaccatggcca gccaaataag agcattttta atgtaaaatt 151380 atgcatgaaa tgtacattcaattttgtctt tgtttactag gatccatgtt ctcacaagct 151440 atgaagaaat gggtgcaaggaaatactgat gaggtaaatc ctacctttag gataaaaaga 151500 tttctgttta taagtgccaccctcatgtaa gtgaggttta aaattttcct tttctttagg 151560 tcccatgttt aagcagcatggcacatttat gttctcttac ccagaatgta ccaagaaagg 151620 gtggtccctt cttaacatctaacaattgcc tggtagtagc agtgaaggta tcttcagtca 151680 gaggctagga ccactgaaggatatacatgc attcaagttt ccatcagcca gcaggcatca 151740 gtaatcagtg tgtagatcaaaagctcaaat gtttccttcc ccactggcag ttttacttca 151800 agtagtggag gcttgcttttttaatagtta attaagtaca ttgagagatg ggaggtgaaa 151860 aaaggaaaat gttttattttgaccatctaa tatgaaagta gttcggtgtt aggtatccag 151920 tagttgacac tggaagacagggaatgacat gttaatattc atagccagag ggtggcccag 151980 gttttttcgt acatgggaatgaaattctta tccaaataag tagaaattat gtgcgtaagc 152040 catttgttaa gagcactgagtatgtgcatc tcgatccatc taatgaataa ccattatcac 152100 cagtttaaat tattttctttaggcccagga agagctagct tggaagattg ctaaaatgat 152160 agtcagtgac attatgcagcaggctcagta tgatcaaccg ttagagaaat ctacaaaggt 152220 aaggatgact tcgttttgtgtaaactaaaa agtattattt tccaggtgta aaaataaaaa 152280 agaacataag gggtttctttgcctttgaag gattaactgc tgtggggatt accttcttat 152340 cataagcaac tagaaaattgacaaactaaa tgaaacaact gtttgcatat attggacaat 152400 gggcaataca gggaaaccatggaaaccaaa cagagcccag tagtcttgct gaacgaaaga 152460 gttaaatatc aaagttcaggccaggtgcag tggctcacgc ctgtaatccc agcactttgg 152520 gaggccaagg cgggtgaatcacttgaggtc aggagttcaa gaccagcctg gccaacatgg 152580 tgaaaccctg tcttagccgggtgtggtggc aggcacctgt aatcccaact atttgggagg 152640 ctgaggcagg agaatcgcttgaaccaggga ggcggaggtt gcagtgagcc gagatcacac 152700 cactgcactc cagcctgggcgacgagcgaa accccatttc aaaaaaaaaa tcaaagttca 152760 gagagctcaa tttgagtagaagttgtagga taaggtagca gaaaagagga agctgcccag 152820 aaagaaagcc gtagagatatttagagagat tcccatggat ccttggccta ggagtgatct 152880 gtatatgtgt ggggtgaaaacgcatgtgtc caggtagaga accccccaga aattagtagg 152940 ctgaatgatt gctggaacatagggctaaga aaagttcatg gccagaagga tctggccaga 153000 gtagagagac ttagtaatacacaaggcatt gggtagtgtc ttcacagagg ttatgcctta 153060 ctactgaaga taaattagtcctagagtaca agcacctgaa ccaagtttca aagcaaattt 153120 ttaaagggtc aaattacctaacaactgcat gccaaaacaa aggcctaacc ctctttacag 153180 taacacaaca aaattcagcacttcacagtg taaagttaga atgtctgacg tccaggctgg 153240 gcgcagtggc tcatgcctgtaatcccagca ctttgggagg ccgaggcagg tagatgacct 153300 gaggtcagga gttcaagaccagcctggcta acatggtgca accccgtctc tattaaaaat 153360 acaaaaactt agccaggcatggtggccggc acctgtgatc ccggctactt gggaggctga 153420 ggcaggagaa ttgcctgaacccaggaggtg aaggttgcag tgagccgaga tcgcaccact 153480 gcactctggt ctgggcaaaaagagcaaaac tcaggctcaa aaaaaaaaaa gaatgtctga 153540 cgtcaatcac aaattaccaagcatgacatg aagttgacct ataaccagga gaaaactcaa 153600 tctatagaaa cagacccagatgtgagaaag atgatgaatt tagcagacaa agaccatcaa 153660 gtggctattt taaatattaaaaatatgttc aagtggccag gtgcagtggc tcatgcctgt 153720 aatcccagca ctttgggaggccaaggtggg taggagttca agaccagctt ggccaatatg 153780 gtgaaacccc ttctctactaaaaatacaaa aaaattagct gggcatggtg gcaggtgcct 153840 atagtcccag ctatatgggaggctgaggca caagaatcac ttgaacccgg gaggtggagg 153900 ttgaggttgc agtaagccgagattgtgcca cttgtactcc agcctggaca acagagtgag 153960 actctgtctc aaaaaaaaaaaaaaaaaagt taaagaaaac aagagtataa tgagaaaaat 154020 gcaaaatagt tttaaaagaaccaaatggaa tttcttaaaa taaaaaatac cagaaatggg 154080 ggccgggcgt ggtagctcacgtctataatc ccagcacttt gtgggggctg aggcaggcag 154140 atcacctgag atcggtagttcaaggccagc ctgaccaaca tggagaaacc tcatctctac 154200 taaaaataca aaattagctgggcgtggtgg cgcattgcct gtaatcccag ctacttggga 154260 ggctgaggca ggagaattgcttgaacccgg gaggcagagg ttgcggtgag ctgagattgc 154320 accagtgcac tccagcttgggccacaagag tgaaactccg tctcaaaaaa aaaacaaaaa 154380 aaaacagtag actcgaagaactagctgagt ttttctttac tttaggcagt aagtgtgacc 154440 ttttgcaggt gactactttagttcctcatg tcctcattag tagatcagag aaattcgaca 154500 ccaaaacccc aaaagaaaaaccccttctaa tcctcattcc atgattttat gaatgcatga 154560 agtcctaggc ctgcgaaggaatactcattc tctttatcct gtgttgatac ctctctgctt 154620 caacctccaa ctcgacatttgcctatagga tgtacttgga cattcagcat aaactacctc 154680 acaccattac tgaattgcttcatgtgcaca tgtcccatgc cacaataccg gggaccttgt 154740 cttccgtgat atttgtccgcagtgctgtga ctacaggagg gagtcagtga atgtctgcat 154800 gtgtgtcttt accatccctcttgaatatgc tctagggtta attcctagaa gtagaattac 154860 tctattgaaa attggcaatatttttcattc taatatctat tgccaacatg ggaaagcaag 154920 tctggatgcc agtccttgttatatgcccct tgggtaagtt acgtaacctc tttaagcttc 154980 tgttcactca tattttaacaaggaaaatta caatatttta cctcacaaaa ttgtagtcag 155040 cttctggctg tcttaaactctggtatatag taaacactaa gtgttggtgt ccatccttaa 155100 tttgtaataa taggtcacttgttagagaaa tgcaccttac cattttcttt tcttttcttt 155160 tttcagttat gactcaaaacttgagataaa ggaaatctgc ttgtgaaaaa taagagaact 155220 tttttccctt ggttggattcttcaacacag ccaatgaaaa cagcactata tttctgatct 155280 gtcactgttg tttccaggagagaatgggag acaatcctag acttccacca taatgcagtt 155340 acctgtaggc ataattgatgcacatgatgt tcacacagtg agagtcttaa agatacaaaa 155400 tggtattgtt tacattactagaaaattatt agttttccaa tggcaataac ccatttatga 155460 gagtgtttta gcctactggaatagacaggg accacatcct ctgggaagca gataagcata 155520 gaactgatac ttgatgcacactcgtagtgg taactcatcc ctaatcagca ttgtaaagca 155580 ggtgccagag gtggtttgctttgtccttcc aaagcaggtg agtcagcccc accgagagcc 155640 aggcagcttt gagtggcagcgtggtgctag cagcttcagc ggaacagggt gagagttaat 155700 tatgcagtct tcttgacagcggcattaatt tggaaggaaa ctgacaagtc atgggtcaag 155760 tttcagtgac ttcctccttcctctgatggc agtatatagt tttcacattt taattcctcc 155820 tcctgagatg cactatacttaaaaccattc tctcccctgc taacagaagg gtgtgaatct 155880 ggtttacttt gagcattaggatttgcccct ttggaattct gcactccagt tacttaactt 155940 tcccttcaga atacatgtggaaagaaagaa agaaatagcg atgactccac ttttgcccct 156000 gtggcacctt gaacaaagcagttcttccca aattatactt tttttttttt taaataaggt 156060 gagcaggatg actggggagagagaaacatt tgactttgac tgcctccccc attctttgct 156120 gtgagctgga aagtgtgcagttggtcgtct ttcttctcct ttctttagga tagtaagaga 156180 ctcactcact gcacttctgctcagttggct tctgcatcgg gatcacacag ccatcagcag 156240 gactgcccag ttggtgagcacactccattg accacgcggc gccagcgctt cctcaatgca 156300 catgattgag aggaaagaaagttctcttag atgttactgc ttttgctcag actttgcaaa 156360 aaaaaaaata tatatatatatgtataaata tataattatt aatcactttt gtccttgaga 156420 aagtcttgaa tgaacagagaatttattcca ttgcaatatt tgattgtata gaggcacact 156480 gtttcatcga cagaagaagcaaaaaggctt tgtgtaagtt tttggtacta tgtaccacct 156540 ctgttattct tttaaagctgaagtattcat gtacttaaac catattatat ttaattgtgt 156600 ttgattttaa aatatatatatatgaattct atttaaaatt gtgtcaactt tctgctttca 156660 gggcatttat ggctcttctgttgaaatata ttgatctttc caaatatttt catttgcttt 156720 ctaaaaaccc agaacatgagccactactgg actttgcctt gtgtttgaag tgtatggcat 156780 aaacccaagg tttttattagtcatctatgc tgtgattaat tcattttgtt cttttaacaa 156840 aatatttcca tccacttcacattgcttcaa tctttaacag aaaagcaata taaaggttat 156900 agaataaaat gtggttttgggcaactcttg ctgcctctgc atgttttgga ataacaattt 156960 ctacaagact ctaggctgtttaaactagtg ctttcagtta agataaattc taatcatttc 157020 tttgtatata cattttgtgcttctgagcta gagatgccaa gtagttgtaa actgcttata 157080 aagagaatag cagcaaatttgagactcggc tacttttttc tgccccacct gctttgagac 157140 acagaagcgg agtgtggcccgaaattatta gccagattta atatttgatc taaagtaggt 157200 ccttgtactc attttaaagttggaatttga ttcctccaac attgagcacc caccatgttc 157260 caggctctgt gcattgtgcccacaaaataa gattccctgg tggagttttt atgggttcaa 157320 ataatcagtt gaacacccttcatctttatc atgttgttga cattgacaca aattgtttaa 157380 aaagaaaaga tattagagagaaagtggtac ctttgtaact tgatgtgtct tcatcattcg 157440 gtaagatttg atgaaagtaaaaagcaaatg tcagccaaat ccagtgaaca gcaataaaac 157500 agggagtaac tttttataactttttctact tggatttcaa cattcagtag agcttttcga 157560 aatgtaagta gtttacagtactggaggttt gactagttca gtaggaattt ggaggggaag 157620 gtcattctga attgtaacaaagtacaaact tctttgctgt tttatttaag tactgagagc 157680 taagcacctg atgaagtgactgacctctct ccagtgacag tgtttgggta cctgcctgac 157740 ttcaggagtg gggtttatgtttctacacag tgaccttttc tctcgccctc tcctccctct 157800 tgcccacaca ccagttgattggacctgggt tgaactcctg atccagacag gcccaagaca 157860 gttcttaatg ttaagaattttggggccggg cacggtggct catgcctgta attgcaacac 157920 tttgggaggc cgagacaggcggatcacttg aggtcagggg ttcgaggcca gcctggccaa 157980 catggtgaaa ccctgtctttactaaaaata caaaaattag ctgggcatgg tggcgcacgc 158040 ctgtaatccc agctacgtgggtggctgaga caggggaatc gcttgaacct ggaggcggag 158100 gttgtgcaat gagccgagaccgtgtcactg cattccagcc tgggtgacag agggagactc 158160 tgtctccaaa aataaaaataagaaaaagaa ttttgggcta ggtgcagtgg ctcacgcctg 158220 taattacagc attttggaaggcccaagatg ggcagatcac ttgaggacag gagttcgaga 158280 ccagcctgga caacatggtgaaactccatc tctactaaaa agacaaaagt tagccagatg 158340 tggtgatggg cacctataatcctagctcct cgggaggctg gggcaggaga atcacttgaa 158400 cccaggaagc agagattgcagtgagccaag atcacatctc tgcactccag cctgggcaac 158460 agagcaagac tctgtctcaaaaaaaaaaga atttggccag gcgcagtggt tcacgcctgt 158520 aatcccagca ctttgggaggccaaggcagg cagatcacga ggtcaggaga tcgagattgt 158580 cctggctaac atggtgaaaccctgtctcta ctaaaaatac aaaacattag ccgggtgtgg 158640 tggtgggcac ctgtagtcccagctactagg gaggctgagg cagaggaagg atgtgaaccc 158700 aggaggcgga gcttgcagtaagccaagatc gtgccactgc actacagtct gggcgacaga 158760 gtgagactcc gtctcaaaaaaaaaaagaat tttggccggg tgcggtggca catgcctgta 158820 gtcccagcac tttgggagaccaaagtgggc ggattacctg aggtcaggag ttcaagacca 158880 gtccggccaa tatggcgaaaccctgtctct tactaaaaaa aatacaaaaa ttagccaggt 158940 gtggtggcgg gcacctggggaggctgaggc agggagaaat gcttgaaccg gggaggcaga 159000 ggttgcagta agccaagatcgtgccactgc actccagagc aagactcttt ctcaaaaaaa 159060 aaaaaaaaag aattttgcatggggaaggag agatactgtt caccatctgg aatggtgctt 159120 ggatgtggca cttacaaaatcaggagccag cactgcatgg acaaacagaa gcatgtgggc 159180 ctgagatagc aggtaccttgataaccctga agacatcctt ggtttctgca tctattcctg 159240 catccttgca ttggactacattaatctgtc agttatcctt ataatgattt ttgatttttt 159300 ttttttgaga tggagtttcgctcttgttgc ccaggctgga gtgcaatggc acgatctcgg 159360 ctcaccacaa cctccacctcccaggttcaa gtgattctgc tgcctcagcc tcctgagtaa 159420 ctgggattac aggcatgcgccaccacacct ggctaatttt gtatttttag tagagacggg 159480 gtttctccat gttggtcaggctggtctcga actcccaacc tcaggtgatc accctgtctc 159540 ggcctcccaa agtgctgggattacaggcgt aagccatggt acccggtctg ttttttgatt 159600 ttttgaaacc agtctgaagtgagttttttt aattacgtga aaggagtttg gctaaaatac 159660 tgccatactg ccctaatgcctaatgattat gtattctcag catgtctgca aagtactgct 159720 gatttctgga gaataatttttctttagtaa acttcactta agtcgtcatg tgtattctct 159780 caaaatggta tcctaacctaatggagctaa aagacacccc ttgtttttat aacaagcagt 159840 tactgaggcc caggaaggggagaagtccct ggcttgtgag atgatcacca ttagaactca 159900 ggcctgggcc agtgccttttcatgcttctc agatccttcc aaagaataat gaagattata 159960 accgctttta gcaattgtaataaacccaga aatagaaagc tttttggtta gagtactggt 160020 agaagtttgg cgggagagataatttttaca aaatttgtaa atacctgcca attctatata 160080 ctaggcaagg tctctggccttgtaaaaccc ctcaaggtta caactttggt ggcccacact 160140 aatagttacc cactgaggccctctccgggt gaacattgag cactagagga agcccctctg 160200 cttgggcagg actgggcgtggtgcagagta ggagcggtga tactgtggat tctgggcagg 160260 tggagatggc cagtgatgtccaataaagga cactggaggg agcagtgtga gtaaaggccc 160320 tgagggcatt catgttcagggagggttgct gcccactggc ttgcttggca cacaggagag 160380 tgggtattcc tgccttagtaactttatgta aacaagtatt tcctcagtct gttcctctca 160440 aactgcctgc tctggcacattcagaatgtc acagaactca cctggatgca ttcagcccct 160500 tgcctaaagg tgacagtgcatctccttccc caccccaccc ctcataccac tgaagcacct 160560 gtcagactgg cccagtctgtgggcaaggag cctagagagg gcttagtttc agcttgaaag 160620 gagctgggat ttaccaagaagcaaatgaga gacgaggatt gcaacaactg tgccatttcc 160680 ccagcttcag ctgactcctgtatattgact gtgccttcag actcatccgt aagtgacccc 160740 aggctggcct ctcccacatcacagtaagaa ttccacacac catacaactt ggaaagaggc 160800 tccagctgaa ggaagccccacacttctttc aagtttttct tagtcttctc ttcttggcaa 160860 agagtacctt ttgtttcttctaattatgta actattggtt tagtaaatat tcacccattc 160920 agtcaccctg taagtggcaggcactgttta cagggacaca ggaaggaata aaaacttgca 160980 ggcaccttgg agcttgcattctattgaaga ggtaatggaa gttgggatag cagctaaact 161040 atgctggtat tggccaggcgcagtggctca cacctgtaat cccagcactt tggaggccaa 161100 ggtgggcaga tcatgaagtcaggagatcga gaccatcctg gctaacatgg tgaaaccccg 161160 tctctactaa aagtaaaaaaaaaaattagc caggtgtggt ggcgggcgcc tgtagtccca 161220 gctacttggg aggctgaggcaggagaatgg tgtgaaccca ggaggcgaag attgcagtga 161280 gccgagatgg caccactgcactccagcctg ggtgacagag cgagactctg tctcagaaaa 161340 aaaaaatatg ctggtagttttgattcaaga tggcctttgg agcccatgat ttaggtctcg 161400 tacccaccaa ggtctactggaaaacatcag gctctcctgc tatagaccca tagggagagc 161460 tgcagccgag agggggagctgaagagaagt gccccttctg tgtcctgtca gcctcatcct 161520 tccgcaagga ccagttgctgtgccactcca ttcacttgct gcaagactgg aggtttttcc 161580 tcaggtgttg agcacctggtttacaagatg tcagcatctt gatgcctgag accatcaagg 161640 caagtctctg aacagggcttaccttagagt aaggcttaga agaggccgta aagtcagtct 161700 cagctccgtg gctctgcagagctttgggac atgtgaattc ttaaaaacaa gactattgta 161760 cagttactat atgcatgcagtataaaatta taaccttgga aaatcctagc tagctgttga 161820 gctaattcca taaagtaatcagctcctgag ttctgcagtg gtaataataa tcagcataat 161880 gagtaaacac tgtgtgtgccaggcagcgtc tcatttgatc cttgtgataa tcttgtaagt 161940 actgattttc tcccttctttaaacaaagtt tttttttttt ttttagagag ggtctcacta 162000 tgttgcccag gctagtcttgaattc 162025 <210> SEQ ID NO 37 <211> LENGTH: 1350 <212> TYPE: DNA <213>ORGANISM: Homo Sapien <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION:(213)...(920) <300> PUBLICATION INFORMATION: <308> DATABASE ACCESSIONNUMBER: GenBank AJ242973 <309> DATABASE ENTRY DATE: 1999-10-26 <400>SEQUENCE: 37 gcggccgcgt cgacgtgaca gccggtacgc ccgggtttgg gcaacctcgattacgggcgg 60 cctccaggcc cgccagcagc gccccgcgcc gcccgcccgc gcccctgccgccccccggtt 120 ccggccgcgg accccactct ctgccgttcc ggctgcggct ccgctgccggtagcgccgtc 180 ccccgggacc acccttcggc tggcgccctc cc atg ctc tcg gcc acccgg agg 233 Met Leu Ser Ala Thr Arg Arg 1 5 gct tgc cag ctc ctc ctc ctccac agc ctc ttt ccc gtc ccg agg atg 281 Ala Cys Gln Leu Leu Leu Leu HisSer Leu Phe Pro Val Pro Arg Met 10 15 20 ggc aac tcg gcc tcg aac atc gtcagc ccc cag gag gcc ttg ccg ggc 329 Gly Asn Ser Ala Ser Asn Ile Val SerPro Gln Glu Ala Leu Pro Gly 25 30 35 cgg aag gaa cag acc cct gta gcg gccaaa cat cat gtc aat ggc aac 377 Arg Lys Glu Gln Thr Pro Val Ala Ala LysHis His Val Asn Gly Asn 40 45 50 55 aga aca gtc gaa cct ttc cca gag ggaaca cag atg gct gta ttt gga 425 Arg Thr Val Glu Pro Phe Pro Glu Gly ThrGln Met Ala Val Phe Gly 60 65 70 atg gga tgt ttc tgg gga gct gaa agg aaattc tgg gtc ttg aaa gga 473 Met Gly Cys Phe Trp Gly Ala Glu Arg Lys PheTrp Val Leu Lys Gly 75 80 85 gtg tat tca act caa gtt ggt ttt gca gga ggctat act tca aat cct 521 Val Tyr Ser Thr Gln Val Gly Phe Ala Gly Gly TyrThr Ser Asn Pro 90 95 100 act tat aaa gaa gtc tgc tca gaa aaa act ggccat gca gaa gtc gtc 569 Thr Tyr Lys Glu Val Cys Ser Glu Lys Thr Gly HisAla Glu Val Val 105 110 115 cga gtg gtg tac cag cca gaa cac atg agt tttgag gaa ctg ctc aag 617 Arg Val Val Tyr Gln Pro Glu His Met Ser Phe GluGlu Leu Leu Lys 120 125 130 135 gtc ttc tgg gag aat cac gac ccg acc caaggt atg cgc cag ggg aac 665 Val Phe Trp Glu Asn His Asp Pro Thr Gln GlyMet Arg Gln Gly Asn 140 145 150 gac cat ggc act cag tac cgc tcg gcc atctac ccg acc tct gcc aag 713 Asp His Gly Thr Gln Tyr Arg Ser Ala Ile TyrPro Thr Ser Ala Lys 155 160 165 caa atg gag gca gcc ctg agc tcc aaa gagaac tac caa aag gtt ctt 761 Gln Met Glu Ala Ala Leu Ser Ser Lys Glu AsnTyr Gln Lys Val Leu 170 175 180 tca gag cac ggc ttc ggc ccc atc act accgac atc cgg gag gga cag 809 Ser Glu His Gly Phe Gly Pro Ile Thr Thr AspIle Arg Glu Gly Gln 185 190 195 act ttc tac tat gcg gaa gac tac cac cagcag tac ctg agc aag aac 857 Thr Phe Tyr Tyr Ala Glu Asp Tyr His Gln GlnTyr Leu Ser Lys Asn 200 205 210 215 ccc aat ggc tac tgc ggc ctt ggg ggcacc ggc gtg tcc tgc cca gtg 905 Pro Asn Gly Tyr Cys Gly Leu Gly Gly ThrGly Val Ser Cys Pro Val 220 225 230 ggt att aaa aaa taa ttgctccccacatggtgggc ctttgaggtt ccagtaaaaa 960 Gly Ile Lys Lys * 235 tgctttcaacaaattgggca atgcttgtgt gattcacaat cgtggcattt aaagtgcaca 1020 aagtacaaaggaatttatac agattgggtt taccgaagta taatctatag gaggcgcgat 1080 ggcaagttgataaaatgtga cttatctcct aataagttat ggtgggagtg gagctgtgcg 1140 gtttcctgtgtcttctgggg tctgagtgaa gatagcaggg atgctgtgtt cacccttctt 1200 ggtagaagctaaggtgtgag ctgggaggtt gctggacagg atgggggacc ccagaagtcc 1260 tttatctgtgctctctgccc gccagtgcct tacaatttgc aaacgtgtat agcctcagtg 1320 actcattcgctgaaatcctt cgctttacca 1350 <210> SEQ ID NO 38 <211> LENGTH: 235 <212>TYPE: PRT <213> ORGANISM: Homo Sapien <400> SEQUENCE: 38 Met Leu Ser AlaThr Arg Arg Ala Cys Gln Leu Leu Leu Leu His Ser 1 5 10 15 Leu Phe ProVal Pro Arg Met Gly Asn Ser Ala Ser Asn Ile Val Ser 20 25 30 Pro Gln GluAla Leu Pro Gly Arg Lys Glu Gln Thr Pro Val Ala Ala 35 40 45 Lys His HisVal Asn Gly Asn Arg Thr Val Glu Pro Phe Pro Glu Gly 50 55 60 Thr Gln MetAla Val Phe Gly Met Gly Cys Phe Trp Gly Ala Glu Arg 65 70 75 80 Lys PheTrp Val Leu Lys Gly Val Tyr Ser Thr Gln Val Gly Phe Ala 85 90 95 Gly GlyTyr Thr Ser Asn Pro Thr Tyr Lys Glu Val Cys Ser Glu Lys 100 105 110 ThrGly His Ala Glu Val Val Arg Val Val Tyr Gln Pro Glu His Met 115 120 125Ser Phe Glu Glu Leu Leu Lys Val Phe Trp Glu Asn His Asp Pro Thr 130 135140 Gln Gly Met Arg Gln Gly Asn Asp His Gly Thr Gln Tyr Arg Ser Ala 145150 155 160 Ile Tyr Pro Thr Ser Ala Lys Gln Met Glu Ala Ala Leu Ser SerLys 165 170 175 Glu Asn Tyr Gln Lys Val Leu Ser Glu His Gly Phe Gly ProIle Thr 180 185 190 Thr Asp Ile Arg Glu Gly Gln Thr Phe Tyr Tyr Ala GluAsp Tyr His 195 200 205 Gln Gln Tyr Leu Ser Lys Asn Pro Asn Gly Tyr CysGly Leu Gly Gly 210 215 220 Thr Gly Val Ser Cys Pro Val Gly Ile Lys Lys225 230 235 <210> SEQ ID NO 39 <211> LENGTH: 481 <212> TYPE: DNA <213>ORGANISM: Homo Sapien <300> PUBLICATION INFORMATION: <308> DATABASEACCESSION NUMBER: GenBank AW195104 <309> DATABASE ENTRY DATE: 1999-11-29<400> SEQUENCE: 39 ggcattattg gactgtaggt ttttattaaa acaaacatttctcatagctc taagcaaagc 60 attagaattc atcaagcgga ctcacatctt ttctctgcacagagaggggc tgaaaaggga 120 gagaaagtcc cttatgtatg tctagatttg gtaaagcgaaggatttcagc gaatgagtca 180 ctgaggctat acacgtttgc aaattgtaag gcactggcgggcagagagca cagataaagg 240 acttctgggg tcccccatcc tgtccagcaa cctcccagctcacaccttag cttctaccaa 300 gaagggtgaa cacagcatcc ctgctatctt cactcagaccccagaaaacc cagggaaacc 360 cgacagctcc actcccacca taacttatta ggagataagtcacattttat caacttgcca 420 tcgcgcctcc tatagattat acttcggtaa acccaatctgtataaattcc tttgtacttt 480 g 481 <210> SEQ ID NO 40 <211> LENGTH: 390<212> TYPE: DNA <213> ORGANISM: Homo Sapien <300> PUBLICATIONINFORMATION: <308> DATABASE ACCESSION NUMBER: GenBank AW874187 <309>DATABASE ENTRY DATE: 2000-05-22 <400> SEQUENCE: 40 ttttttttat tggactgtaggtttttatta aaacaaacat ttctcatagc tctaagcaaa 60 gcattagaat tcatcaagcggactcacatc ttttctctgc acagagaggg ctgaaaaggg 120 agagaaagcc ccttatgtatgtctagattt ggtaaagcga aggatttcag cgaatgagtc 180 actgaggcta tacacgtttgcaaattgtaa ggcactggcg ggcagagagc acagataaag 240 gacttttggg ggtcccccattcctgtccag caacctccca gctcacacct tagcttctac 300 caagaagggg tgaacacagcatccctgcta tcttcactca gacccccaga agacacagga 360 aaccgcacag ctccactcccaccataactt 390 <210> SEQ ID NO 41 <211> LENGTH: 43 <212> TYPE: DNA <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Oligonucleotide Primer <400> SEQUENCE: 41 agcggataac aatttcacacagggagctag cttggaagat tgc 43 <210> SEQ ID NO 42 <211> LENGTH: 22 <212>TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide Primer <400> SEQUENCE: 42 gtccaatatatgcaaacagt tg 22 <210> SEQ ID NO 43 <211> LENGTH: 23 <212> TYPE: DNA<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide Primer <400> SEQUENCE: 43 agcggataacaatttcacac agg 23 <210> SEQ ID NO 44 <211> LENGTH: 18 <212> TYPE: DNA<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide Primer <400> SEQUENCE: 44 actgagcctgctgcataa 18 <210> SEQ ID NO 45 <211> LENGTH: 21 <212> TYPE: DNA <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Oligonucleotide Primer <400> SEQUENCE: 45 tctcaatcat gtgcattgag g 21<210> SEQ ID NO 46 <211> LENGTH: 43 <212> TYPE: DNA <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Oligonucleotide Primer <400> SEQUENCE: 46 agcggataac aatttcacacagggatcaca cagccatcag cag 43 <210> SEQ ID NO 47 <211> LENGTH: 23 <212>TYPE: DNA <213> ORGANISM: oligonucleotide primer <400> SEQUENCE: 47agcggataac aatttcacac agg 23 <210> SEQ ID NO 48 <211> LENGTH: 18 <212>TYPE: DNA <213> ORGANISM: Oligonucleotide primer <400> SEQUENCE: 48ctggcgccac gtggtcaa 18 <210> SEQ ID NO 49 <211> LENGTH: 20 <212> TYPE:DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide Primer <400> SEQUENCE: 49 tttctctgcacagagagggc 20 <210> SEQ ID NO 50 <211> LENGTH: 44 <212> TYPE: DNA <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Oligonucleotide Primer <400> SEQUENCE: 50 agcggataac aatttcacacagggctgaaa tccttcgctt tacc 44 <210> SEQ ID NO 51 <211> LENGTH: 23 <212>TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide Primer <400> SEQUENCE: 51 agcggataacaatttcacac agg 23 <210> SEQ ID NO 52 <211> LENGTH: 18 <212> TYPE: DNA<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide Primer <400> SEQUENCE: 52 ctgaaaagggagagaaag 18 <210> SEQ ID NO 53 <211> LENGTH: 20 <212> TYPE: DNA <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Oligonucleotide Primer <400> SEQUENCE: 53 tcccaaagtg ctggaattac 20 <210>SEQ ID NO 54 <211> LENGTH: 22 <212> TYPE: DNA <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Oligonucleotide Primer<400> SEQUENCE: 54 gtccaatata tgcaaacagt tg 22 <210> SEQ ID NO 55 <211>LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Oligonucleotide Primer <400> SEQUENCE:55 cccacagcag ttaatccttc 20 <210> SEQ ID NO 56 <211> LENGTH: 18 <212>TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 56 gcgctcctgtcggtgcca 18 <210> SEQ ID NO 57 <211> LENGTH: 18 <212> TYPE: DNA <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Oligonucleotide primer <400> SEQUENCE: 57 gcctgactgg tggggccc 18 <210>SEQ ID NO 58 <211> LENGTH: 15 <212> TYPE: DNA <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Oligonucleotide primer<400> SEQUENCE: 58 catgcatgca cggtc 15 <210> SEQ ID NO 59 <211> LENGTH:30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 59cagagagtac ccctcgaccg tgcatgcatg 30 <210> SEQ ID NO 60 <211> LENGTH: 15<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 60 catgcatgcacggtt 15 <210> SEQ ID NO 61 <211> LENGTH: 30 <212> TYPE: DNA <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Oligonucleotide primer <400> SEQUENCE: 61 gtacgtacgt gccaactccccatgagagac 30 <210> SEQ ID NO 62 <211> LENGTH: 14 <212> TYPE: DNA <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Oligonucleotide primer <400> SEQUENCE: 62 catgcatgca cggt 14 <210> SEQID NO 63 <211> LENGTH: 18 <212> TYPE: DNA <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Oligonucleotide primer<400> SEQUENCE: 63 gcctgactgg tggggccc 18 <210> SEQ ID NO 64 <211>LENGTH: 26 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE:64 gtgctgcagg tgtaaacttg taccag 26 <210> SEQ ID NO 65 <211> LENGTH: 28<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 65 cacggatccggtagcagcgg tagagttg 28 <210> SEQ ID NO 66 <211> LENGTH: 19 <212> TYPE:DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 66 actgggcatgtggagacag 19 <210> SEQ ID NO 67 <211> LENGTH: 18 <212> TYPE: DNA <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Oligonucleotide primer <400> SEQUENCE: 67 gcactttctt gccatgag 18 <210>SEQ ID NO 68 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Oligonucleotide primer<400> SEQUENCE: 68 tcagtcacga cgtt 14 <210> SEQ ID NO 69 <211> LENGTH:14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 69cggataacaa tttc 14 <210> SEQ ID NO 70 <211> LENGTH: 37 <212> TYPE: DNA<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 70 caatttcatcgctggatgca atctgggcta tgagatc 37 <210> SEQ ID NO 71 <211> LENGTH: 37<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 71 caatttcacacagcggatgc ttcttttggc tctgact 37 <210> SEQ ID NO 72 <211> LENGTH: 40<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 72 tcagtcacgacgttggatgc caataaaagt gactctcagc 40 <210> SEQ ID NO 73 <211> LENGTH: 37<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 73 cggataacaatttcggatgc actgggagca ttgaggc 37 <210> SEQ ID NO 74 <211> LENGTH: 38<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 74 tcagtcacgacgttggatga gcagatccct ggacaggc 38 <210> SEQ ID NO 75 <211> LENGTH: 38<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 75 cggataacaatttcggatgg acaaaatacc tgtattcc 38 <210> SEQ ID NO 76 <211> LENGTH: 36<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 76 tcagtcacgacgttggatgc agagcagctc cgagtc 36 <210> SEQ ID NO 77 <211> LENGTH: 32<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 77 cagcggtgatcattggatgc aggaagctct gg 32 <210> SEQ ID NO 78 <211> LENGTH: 38 <212>TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 78 tcagtcacgacgttggatgc ccacatgcca cccactac 38 <210> SEQ ID NO 79 <211> LENGTH: 35<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 79 cggataacaatttcggatgc ccgtcaggta ccacg 35 <210> SEQ ID NO 80 <211> LENGTH: 37 <212>TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 80 tcagtcacgacgttggatgc ccacagtgga gcttcag 37 <210> SEQ ID NO 81 <211> LENGTH: 22<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 81 gctcataccttgcaggatga cg 22 <210> SEQ ID NO 82 <211> LENGTH: 36 <212> TYPE: DNA<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 82 tcagtcacgacgttggatga ccagctgttc gtgttc 36 <210> SEQ ID NO 83 <211> LENGTH: 34<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 83 tacatggagttcggggatgc acacggcgac tctc 34 <210> SEQ ID NO 84 <211> LENGTH: 40 <212>TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 84 tcagtcacgacgttggatgg ggaagagcag agatatacgt 40 <210> SEQ ID NO 85 <211> LENGTH: 29<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 85 gaggggctgatccaggatgg gtgctccac 29 <210> SEQ ID NO 86 <211> LENGTH: 30 <212> TYPE:DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 86 tgaagcacttgaaggatgag ggtgtctgcg 30 <210> SEQ ID NO 87 <211> LENGTH: 38 <212> TYPE:DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 87 cggataacaatttcggatgc tgcgtgatga tgaaatcg 38 <210> SEQ ID NO 88 <211> LENGTH: 26<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 88 gatgaagctcccaggatgcc agaggc 26 <210> SEQ ID NO 89 <211> LENGTH: 27 <212> TYPE: DNA<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 89 gccgccggtgtaggatgctg ctggtgc 27 <210> SEQ ID NO 90 <211> LENGTH: 31 <212> TYPE:DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide Template <400> SEQUENCE: 90 cgcagggtttcctcgtcgca ctgggcatgt g 31 <210> SEQ ID NO 91 <211> LENGTH: 43 <212>TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Biotinylatd primer <400> SEQUENCE: 91 tgcttatccc tgtagctaccctgtcttggc cttgcagatc caa 43 <210> SEQ ID NO 92 <211> LENGTH: 42 <212>TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Oligonucleotide primer <400> SEQUENCE: 92 agcggataacaatttcacac aggccatcac accgcggtac tg 42 <210> SEQ ID NO 93 <211> LENGTH:44 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE: 93cccagtcacg acgttgtaaa acgtcttggc cttgcagatc caag 44 <210> SEQ ID NO 94<211> LENGTH: 42 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Oligonucleotide primer <400>SEQUENCE: 94 agcggataac aatttcacac aggccatcac accgcggtac tg 42 <210> SEQID NO 95 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Oligonucleotide primer<400> SEQUENCE: 95 ctccagctgg gcaggagtgc 20 <210> SEQ ID NO 96 <211>LENGTH: 17 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Oligonucleotide primer <400> SEQUENCE:96 cacttcagtc gctccct 17 <210> SEQ ID NO 97 <211> LENGTH: 23 <212> TYPE:DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Biotinylated primer <400> SEQUENCE: 97 cccagtcacgacgttgtaaa acg 23 <210> SEQ ID NO 98 <211> LENGTH: 100 <212> TYPE: DNA<213> ORGANISM: Homo sapien <400> SEQUENCE: 98 cctttgagaa agggctctgcttgagttgta gaaagaaccg ctgcaacaat ctgggctatg 60 agatcaataa agtcagagccaaaagaagca gcaaaatgta 100 <210> SEQ ID NO 99 <211> LENGTH: 100 <212>TYPE: DNA <213> ORGANISM: Homo sapien <400> SEQUENCE: 99 cctttgagaaagggctctgc ttgagttgta gaaagaaccg ctgcaacaat ctgggctatg 60 agatcagtaaagtcagagcc aaaagaagca gcaaaatgta 100 <210> SEQ ID NO 100 <211> LENGTH:100 <212> TYPE: DNA <213> ORGANISM: Homo sapien <400> SEQUENCE: 100gaattatttt tgtgtttcta aaactatggt tcccaataaa agtgactctc agcgagcctc 60aatgctccca gtgctattca tgggcagctc tctgggctca 100 <210> SEQ ID NO 101<211> LENGTH: 100 <212> TYPE: DNA <213> ORGANISM: Homo sapien <400>SEQUENCE: 101 gaattatttt tgtgtttcta aaactatggt tcccaataaa agtgactctcagcaagcctc 60 aatgctccca gtgctattca tgggcagctc tctgggctca 100 <210> SEQID NO 102 <211> LENGTH: 84 <212> TYPE: DNA <213> ORGANISM: Homo sapien<400> SEQUENCE: 102 taataggact acttctaatc tgtaagagca gatccctggacaggcgagga atacaggtat 60 tttgtccttg aagtaacctt tcag 84 <210> SEQ ID NO103 <211> LENGTH: 84 <212> TYPE: DNA <213> ORGANISM: Homo sapien <400>SEQUENCE: 103 taataggact acttctaatc tgtaagagca gatccctgga caggcaaggaatacaggtat 60 tttgtccttg aagtaacctt tcag 84 <210> SEQ ID NO 104 <211>LENGTH: 100 <212> TYPE: DNA <213> ORGANISM: Homo sapien <400> SEQUENCE:104 ctcaccatgg gcatttgatt gcagagcagc tccgagtccg tccagagctt cctgcagtca 60atgatcaccg ctgtgggcat ccctgaggtc atgtctcgta 100 <210> SEQ ID NO 105<211> LENGTH: 100 <212> TYPE: DNA <213> ORGANISM: Homo sapien <400>SEQUENCE: 105 ctcaccatgg gcatttgatt gcagagcagc tccgagtcca tccagagcttcctgcagtca 60 atgatcaccg ctgtgggcat ccctgaggtc atgtctcgta 100 <210> SEQID NO 106 <211> LENGTH: 100 <212> TYPE: DNA <213> ORGANISM: Homo sapien<400> SEQUENCE: 106 agcaaggact cctgcaaggg ggacagtgga ggcccacatgccacccacta ccagggcacg 60 tggtacctga cgggcatcgt cagctggggc cagggctgcg 100<210> SEQ ID NO 107 <211> LENGTH: 100 <212> TYPE: DNA <213> ORGANISM:Homo sapien <400> SEQUENCE: 107 agcaaggact cctgcaaggg ggacagtggaggcccacatg ccacccacta ccggggcacg 60 tggtacctga cgggcatcgt cagctggggccagggctgcg 100 <210> SEQ ID NO 108 <211> LENGTH: 100 <212> TYPE: DNA<213> ORGANISM: Hom sapien <400> SEQUENCE: 108 caataactct aatgcagcggaagatgacct gcccacagtg gagcttcagg gcgtggtgcc 60 ccggggcgtc aacctgcaaggtatgagcat accccccttc 100 <210> SEQ ID NO 109 <211> LENGTH: 100 <212>TYPE: DNA <213> ORGANISM: Homo sapien <400> SEQUENCE: 109 caataactctaatgcagcgg aagatgacct gcccacagtg gagcttcagg gcttggtgcc 60 ccggggcgtcaacctgcaag gtatgagcat accccccttc 100 <210> SEQ ID NO 110 <211> LENGTH:100 <212> TYPE: DNA <213> ORGANISM: Homo sapien <400> SEQUENCE: 110ttgaagcttt gggctacgtg gatgaccagc tgttcgtgtt ctatgatcat gagagtcgcc 60gtgtggagcc ccgaactcca tgggtttcca gtagaatttc 100 <210> SEQ ID NO 111<211> LENGTH: 100 <212> TYPE: DNA <213> ORGANISM: Homo sapien <400>SEQUENCE: 111 ttgaagcttt gggctacgtg gatgaccagc tgttcgtgtt ctatgatgatgagagtcgcc 60 gtgtggagcc ccgaactcca tgggtttcca gtagaatttc 100 <210> SEQID NO 112 <211> LENGTH: 100 <212> TYPE: DNA <213> ORGANISM: Homo sapien<400> SEQUENCE: 112 ggataacctt ggctgtaccc cctggggaag agcagagatatacgtgccag gtggagcacc 60 caggcctgga tcagcccctc attgtgatct gggagccctc 100<210> SEQ ID NO 113 <211> LENGTH: 100 <212> TYPE: DNA <213> ORGANISM:Homo sapien <400> SEQUENCE: 113 ggataacctt ggctgtaccc cctggggaagagcagagata tacgtaccag gtggagcacc 60 caggcctgga tcagcccctc attgtgatctgggagccctc 100 <210> SEQ ID NO 114 <211> LENGTH: 80 <212> TYPE: DNA<213> ORGANISM: Homo sapien <400> SEQUENCE: 114 tgaagcactt gaaggagaaggtgtctgcgg gagccgattt catcatcacg cagcttttct 60 ttgaggctga cacattcttc 80<210> SEQ ID NO 115 <211> LENGTH: 80 <212> TYPE: DNA <213> ORGANISM:Homo sapien <400> SEQUENCE: 115 tgaagcactt gaaggagaag gtgtctgcgggagtcgattt catcatcacg cagcttttct 60 ttgaggctga cacattcttc 80 <210> SEQID NO 116 <211> LENGTH: 80 <212> TYPE: DNA <213> ORGANISM: Homo sapien<400> SEQUENCE: 116 tccagatgaa gctcccagaa tgccagaggc tgctccccgcgtggcccctg caccagcagc 60 tcctacaccg gcggcccctg 80 <210> SEQ ID NO 117<211> LENGTH: 80 <212> TYPE: DNA <213> ORGANISM: Homo sapien <400>SEQUENCE: 117 tccagatgaa gctcccagaa tgccagaggc tgctcccccc gtggcccctgcaccagcagc 60 tcctacaccg gcggcccctg 80 <210> SEQ ID NO 118 <211> LENGTH:48 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Hair pin structure <400> SEQUENCE: 118cagagagtac ccctcaaccg tgcatgcatg aaacatgcat gcacggtt 48

What is claimed is:
 1. A high throughput method of determiningfrequencies of genetic variations, comprising: selecting a healthytarget population and a genetic variation to be assessed; pooling aplurality of samples of biopolymers obtained from members of thepopulation; determining or detecting the biopolymer that comprises thevariation by mass spectrometry; obtaining a mass spectrum or a digitalrepresentation thereof; and determining the frequency of the variationin the population.
 2. The method of claim 1, wherein: the variation isselected from the group consisting of an allelic variation, apost-translational modification, a nucleic modification, a label, a massmodification of a nucleic acid and methylation; and/or the biopolymer isa nucleic acid, a protein, a polysaccharide, a lipid, a small organicmetabolite or intermediate, wherein the concentration of biopolymer ofinterest is the same in each of the samples; and/or the frequency isdetermined by assessing the method comprising determining the area underthe peak in the mass spectrum or digital representation thereofcorresponding to the mass of the biopolymer comprising the genomicvariation.
 3. The method of claim 2, wherein the method for determiningthe frequency is effected by determining the ratio of the signal or thedigital representation thereof to the total area of the entire massspectrum, which is corrected for background.